Ruchika Gutt, MD

Radiation therapy, along with surgery and systemic therapy, is a primary therapeutic modality for cancer management. At least half of cancer patients receive radiation as part of their treatment regimen.¹ Multiple studies demonstrate that radiotherapy is underutilized worldwide.² One reason for underutilization of radiotherapy globally is poor access to this treatment modality. Factors that contribute to poor access include long wait times for consultation, delays in treatment initiation, distance to a treatment facility, and poor coordination of care.

Taskforce Findings

The presence of onsite radiation oncology and its impact on utilization of radiotherapy is poorly studied. The Veterans Health Administration (VHA) Palliative Radiotherapy Taskforce recently conducted a survey to determine the barriers to referral and timeliness of treatment for palliative radiotherapy within the VHA.³ Key findings of this study comparing centers with onsite radiation departments with centers without onsite radiation departments include:

a. Radiation consults are more likely to be completed within 1 week of consult request at centers with onsite radiation therapy (68% vs 31%, respectively; P = .01).

b. Centers with onsite radiation therapy more frequently deliver emergent treatment within 24 hours for patients with spinal cord compression, an emergency condition in which prompt radiation can prevent or minimize long-term neurologic disability (94% vs 70%, respectively; P = .01).

c. Referring practitioners with onsite radiation departments are less likely to report difficulty contacting a radiation oncologist as a barrier to referral for palliative radiotherapy (0% vs 20%, respectively; P = .006).

d. Referring practitioners with onsite radiotherapy report patient travel as a barrier to referral for palliative radiotherapy less frequently (28% vs 71%, respectively; P < .001).

e. Practitioners with onsite radiation oncology departments are more likely to have multidisciplinary tumor boards (31% vs 3%, respectively; P = .01) and are more likely to be influenced by radiation oncology recommendations at tumor boards (69% vs 44%, respectively; P = .02).

Based on the findings of this study, the VHA Palliative Radiotherapy Taskforce has prepared this consensus statement regarding the importance of onsite radiation oncology departments at VHA medical centers. More information regarding our 5 key findings and their implications for patient care are as follows:

Timeliness of Radiation Oncology Consultation

Delays in radiation oncology consultation, which can also delay treatment initiation, are associated with poor satisfaction among both patients and referring clinicians.⁴ Wait times have been identified as a barrier to utilization of radiotherapy by both patients and clinicians.^5,6 Furthermore, delays in initiation of definitive therapy have been associated with worse outcomes, including worse overall survival.^7,8 Our survey study demonstrates that consults for palliative radiotherapy are occurring in a more timely manner at centers with onsite radiation departments. Radiation oncology consults are more frequently completed within 1 week at centers with onsite radiation oncology departments compared with centers without onsite radiation oncology departments (68% vs 31%, P = .01). This trend would likely be seen for nonpalliative, definitive cases as well. The presence of radiation oncology departments onsite at VHA medical centers is an important component of timely care for veterans to optimize outcomes of cancer treatment.

Timely Delivery of Radiotherapy for Oncologic Emergencies

There are a few scenarios in which emergent radiation treatment, within 24 hours, is indicated. These include malignant spinal cord compression, uncal herniation from brain metastasis, superior vena cava syndrome, and tumor hemorrhage.⁹ Studies on management of metastatic spinal cord compression demonstrate that delays in treatment are associated with reduced ambulation¹⁰ as well as loss of sphincter function and incontinence.¹¹

Our study demonstrates that VHA medical centers with onsite radiotherapy more frequently deliver radiotherapy within 24 hours for patients with metastatic spinal cord compression. This timely delivery of treatment is critical to optimizing functional status and quality of life in patients requiring treatment for oncologic emergencies. Revisiting treatment pathways for such situations at regular intervals is crucial given that residents and staff may rotate and be unfamiliar with emergency protocols.

Communication With Radiation Oncologists

Several studies have demonstrated that the inability to contact a radiation oncologist and poor communication result in decreased referrals for palliative radiotherapy.^12,13 Our study demonstrates that onsite radiation oncology is associated with improved ability to contact a radiation oncologist. About 20% of clinicians at facilities without onsite radiation oncology reported difficulty contacting a radiation oncologist, compared with 0% at facilities with onsite radiation departments (P = .006).

It is possible that increased radiation oncology presence at VHA medical centers, through attenuation of barriers related to contacting a radiation oncologist and improved communication, would lead to increased use of radiotherapy. Increased communication between referring clinicians and radiation oncologists also can help with education of those clinicians making the referral. Since knowledge gaps have been identified in multiple studies as a barrier to referral for radiotherapy, such communication and increased education on the role of radiotherapy could increase use.^12-14

Patient Travel

Patient ability to travel was the most commonly reported barrier (81%) to referral for palliative radiotherapy in our study. Travel time and transportation difficulties have been established in multiple studies as barriers to radiotherapy for both definitive and palliative management.^15-18 Travel for radiotherapy was much less frequently reported as a barrier among respondents with onsite radiation oncology departments compared with those without onsite radiation departments (28% vs 71%, respectively; P < .001).

It is therefore possible that expansion of VHA radiation oncology services, allowing for provision of onsite radiotherapy at more VHA facilities, would reduce travel burden. Increasing travel accommodations for patients and provision of patient lodging on hospital campuses, which is already offered at some VHA medical centers (ie, Fisher House Foundation), could also help attenuate this barrier.

Multidisciplinary Tumor Boards

Our study demonstrates that centers with onsite radiation departments more frequently hold multidisciplinary tumor boards compared with centers without radiation departments (31% vs 3%, respectively; P = .01). Multidisciplinary tumor boards allow subspecialties to meet regularly to communicate about patient care and can help mitigate barriers related to communication and education of the referring health care practitioners.

As cases are discussed in multidisciplinary tumor boards, health care practitioners have the opportunity to make recommendations and provide education on potential benefits and/or downsides of treatments offered by their respective specialties. Several studies have demonstrated that cases discussed at multidisciplinary tumor boards are more likely to be referred for radiation therapy.^19-21 Furthermore, multidisciplinary tumor boards have been associated with improved treatment outcomes.²²

Conclusions

In this consensus statement the VHA Palliative Radiotherapy Taskforce recommends the optimization of use of radiotherapy within the VHA. Radiation oncology services should be maintained where present in the VHA, with consideration for expansion of services to additional facilities. Telehealth should be used to expedite consults and treatment. Hypofractionation should be used, when appropriate, to ease travel burden. Options for transportation services and onsite housing, or hospitalization, should be understood by practitioners and offered to patients to mitigate barriers related to travel.

Radiation therapy, along with surgery and systemic therapy, is a primary therapeutic modality for cancer management. At least half of cancer patients receive radiation as part of their treatment regimen.¹ Multiple studies demonstrate that radiotherapy is underutilized worldwide.² One reason for underutilization of radiotherapy globally is poor access to this treatment modality. Factors that contribute to poor access include long wait times for consultation, delays in treatment initiation, distance to a treatment facility, and poor coordination of care.

Taskforce Findings

The presence of onsite radiation oncology and its impact on utilization of radiotherapy is poorly studied. The Veterans Health Administration (VHA) Palliative Radiotherapy Taskforce recently conducted a survey to determine the barriers to referral and timeliness of treatment for palliative radiotherapy within the VHA.³ Key findings of this study comparing centers with onsite radiation departments with centers without onsite radiation departments include:

a. Radiation consults are more likely to be completed within 1 week of consult request at centers with onsite radiation therapy (68% vs 31%, respectively; P = .01).

b. Centers with onsite radiation therapy more frequently deliver emergent treatment within 24 hours for patients with spinal cord compression, an emergency condition in which prompt radiation can prevent or minimize long-term neurologic disability (94% vs 70%, respectively; P = .01).

c. Referring practitioners with onsite radiation departments are less likely to report difficulty contacting a radiation oncologist as a barrier to referral for palliative radiotherapy (0% vs 20%, respectively; P = .006).

d. Referring practitioners with onsite radiotherapy report patient travel as a barrier to referral for palliative radiotherapy less frequently (28% vs 71%, respectively; P < .001).

e. Practitioners with onsite radiation oncology departments are more likely to have multidisciplinary tumor boards (31% vs 3%, respectively; P = .01) and are more likely to be influenced by radiation oncology recommendations at tumor boards (69% vs 44%, respectively; P = .02).

Based on the findings of this study, the VHA Palliative Radiotherapy Taskforce has prepared this consensus statement regarding the importance of onsite radiation oncology departments at VHA medical centers. More information regarding our 5 key findings and their implications for patient care are as follows:

Timeliness of Radiation Oncology Consultation

Delays in radiation oncology consultation, which can also delay treatment initiation, are associated with poor satisfaction among both patients and referring clinicians.⁴ Wait times have been identified as a barrier to utilization of radiotherapy by both patients and clinicians.^5,6 Furthermore, delays in initiation of definitive therapy have been associated with worse outcomes, including worse overall survival.^7,8 Our survey study demonstrates that consults for palliative radiotherapy are occurring in a more timely manner at centers with onsite radiation departments. Radiation oncology consults are more frequently completed within 1 week at centers with onsite radiation oncology departments compared with centers without onsite radiation oncology departments (68% vs 31%, P = .01). This trend would likely be seen for nonpalliative, definitive cases as well. The presence of radiation oncology departments onsite at VHA medical centers is an important component of timely care for veterans to optimize outcomes of cancer treatment.

Timely Delivery of Radiotherapy for Oncologic Emergencies

There are a few scenarios in which emergent radiation treatment, within 24 hours, is indicated. These include malignant spinal cord compression, uncal herniation from brain metastasis, superior vena cava syndrome, and tumor hemorrhage.⁹ Studies on management of metastatic spinal cord compression demonstrate that delays in treatment are associated with reduced ambulation¹⁰ as well as loss of sphincter function and incontinence.¹¹

Our study demonstrates that VHA medical centers with onsite radiotherapy more frequently deliver radiotherapy within 24 hours for patients with metastatic spinal cord compression. This timely delivery of treatment is critical to optimizing functional status and quality of life in patients requiring treatment for oncologic emergencies. Revisiting treatment pathways for such situations at regular intervals is crucial given that residents and staff may rotate and be unfamiliar with emergency protocols.

Communication With Radiation Oncologists

Several studies have demonstrated that the inability to contact a radiation oncologist and poor communication result in decreased referrals for palliative radiotherapy.^12,13 Our study demonstrates that onsite radiation oncology is associated with improved ability to contact a radiation oncologist. About 20% of clinicians at facilities without onsite radiation oncology reported difficulty contacting a radiation oncologist, compared with 0% at facilities with onsite radiation departments (P = .006).

It is possible that increased radiation oncology presence at VHA medical centers, through attenuation of barriers related to contacting a radiation oncologist and improved communication, would lead to increased use of radiotherapy. Increased communication between referring clinicians and radiation oncologists also can help with education of those clinicians making the referral. Since knowledge gaps have been identified in multiple studies as a barrier to referral for radiotherapy, such communication and increased education on the role of radiotherapy could increase use.^12-14

Patient Travel

Patient ability to travel was the most commonly reported barrier (81%) to referral for palliative radiotherapy in our study. Travel time and transportation difficulties have been established in multiple studies as barriers to radiotherapy for both definitive and palliative management.^15-18 Travel for radiotherapy was much less frequently reported as a barrier among respondents with onsite radiation oncology departments compared with those without onsite radiation departments (28% vs 71%, respectively; P < .001).

It is therefore possible that expansion of VHA radiation oncology services, allowing for provision of onsite radiotherapy at more VHA facilities, would reduce travel burden. Increasing travel accommodations for patients and provision of patient lodging on hospital campuses, which is already offered at some VHA medical centers (ie, Fisher House Foundation), could also help attenuate this barrier.

Multidisciplinary Tumor Boards

Our study demonstrates that centers with onsite radiation departments more frequently hold multidisciplinary tumor boards compared with centers without radiation departments (31% vs 3%, respectively; P = .01). Multidisciplinary tumor boards allow subspecialties to meet regularly to communicate about patient care and can help mitigate barriers related to communication and education of the referring health care practitioners.

As cases are discussed in multidisciplinary tumor boards, health care practitioners have the opportunity to make recommendations and provide education on potential benefits and/or downsides of treatments offered by their respective specialties. Several studies have demonstrated that cases discussed at multidisciplinary tumor boards are more likely to be referred for radiation therapy.^19-21 Furthermore, multidisciplinary tumor boards have been associated with improved treatment outcomes.²²

Conclusions

In this consensus statement the VHA Palliative Radiotherapy Taskforce recommends the optimization of use of radiotherapy within the VHA. Radiation oncology services should be maintained where present in the VHA, with consideration for expansion of services to additional facilities. Telehealth should be used to expedite consults and treatment. Hypofractionation should be used, when appropriate, to ease travel burden. Options for transportation services and onsite housing, or hospitalization, should be understood by practitioners and offered to patients to mitigate barriers related to travel.

Radiation therapy, along with surgery and systemic therapy, is a primary therapeutic modality for cancer management. At least half of cancer patients receive radiation as part of their treatment regimen.¹ Multiple studies demonstrate that radiotherapy is underutilized worldwide.² One reason for underutilization of radiotherapy globally is poor access to this treatment modality. Factors that contribute to poor access include long wait times for consultation, delays in treatment initiation, distance to a treatment facility, and poor coordination of care.

Taskforce Findings

The presence of onsite radiation oncology and its impact on utilization of radiotherapy is poorly studied. The Veterans Health Administration (VHA) Palliative Radiotherapy Taskforce recently conducted a survey to determine the barriers to referral and timeliness of treatment for palliative radiotherapy within the VHA.³ Key findings of this study comparing centers with onsite radiation departments with centers without onsite radiation departments include:

a. Radiation consults are more likely to be completed within 1 week of consult request at centers with onsite radiation therapy (68% vs 31%, respectively; P = .01).

b. Centers with onsite radiation therapy more frequently deliver emergent treatment within 24 hours for patients with spinal cord compression, an emergency condition in which prompt radiation can prevent or minimize long-term neurologic disability (94% vs 70%, respectively; P = .01).

c. Referring practitioners with onsite radiation departments are less likely to report difficulty contacting a radiation oncologist as a barrier to referral for palliative radiotherapy (0% vs 20%, respectively; P = .006).

d. Referring practitioners with onsite radiotherapy report patient travel as a barrier to referral for palliative radiotherapy less frequently (28% vs 71%, respectively; P < .001).

e. Practitioners with onsite radiation oncology departments are more likely to have multidisciplinary tumor boards (31% vs 3%, respectively; P = .01) and are more likely to be influenced by radiation oncology recommendations at tumor boards (69% vs 44%, respectively; P = .02).

Based on the findings of this study, the VHA Palliative Radiotherapy Taskforce has prepared this consensus statement regarding the importance of onsite radiation oncology departments at VHA medical centers. More information regarding our 5 key findings and their implications for patient care are as follows:

Timeliness of Radiation Oncology Consultation

Delays in radiation oncology consultation, which can also delay treatment initiation, are associated with poor satisfaction among both patients and referring clinicians.⁴ Wait times have been identified as a barrier to utilization of radiotherapy by both patients and clinicians.^5,6 Furthermore, delays in initiation of definitive therapy have been associated with worse outcomes, including worse overall survival.^7,8 Our survey study demonstrates that consults for palliative radiotherapy are occurring in a more timely manner at centers with onsite radiation departments. Radiation oncology consults are more frequently completed within 1 week at centers with onsite radiation oncology departments compared with centers without onsite radiation oncology departments (68% vs 31%, P = .01). This trend would likely be seen for nonpalliative, definitive cases as well. The presence of radiation oncology departments onsite at VHA medical centers is an important component of timely care for veterans to optimize outcomes of cancer treatment.

Timely Delivery of Radiotherapy for Oncologic Emergencies

There are a few scenarios in which emergent radiation treatment, within 24 hours, is indicated. These include malignant spinal cord compression, uncal herniation from brain metastasis, superior vena cava syndrome, and tumor hemorrhage.⁹ Studies on management of metastatic spinal cord compression demonstrate that delays in treatment are associated with reduced ambulation¹⁰ as well as loss of sphincter function and incontinence.¹¹

Our study demonstrates that VHA medical centers with onsite radiotherapy more frequently deliver radiotherapy within 24 hours for patients with metastatic spinal cord compression. This timely delivery of treatment is critical to optimizing functional status and quality of life in patients requiring treatment for oncologic emergencies. Revisiting treatment pathways for such situations at regular intervals is crucial given that residents and staff may rotate and be unfamiliar with emergency protocols.

Communication With Radiation Oncologists

Several studies have demonstrated that the inability to contact a radiation oncologist and poor communication result in decreased referrals for palliative radiotherapy.^12,13 Our study demonstrates that onsite radiation oncology is associated with improved ability to contact a radiation oncologist. About 20% of clinicians at facilities without onsite radiation oncology reported difficulty contacting a radiation oncologist, compared with 0% at facilities with onsite radiation departments (P = .006).

It is possible that increased radiation oncology presence at VHA medical centers, through attenuation of barriers related to contacting a radiation oncologist and improved communication, would lead to increased use of radiotherapy. Increased communication between referring clinicians and radiation oncologists also can help with education of those clinicians making the referral. Since knowledge gaps have been identified in multiple studies as a barrier to referral for radiotherapy, such communication and increased education on the role of radiotherapy could increase use.^12-14

Patient Travel

Patient ability to travel was the most commonly reported barrier (81%) to referral for palliative radiotherapy in our study. Travel time and transportation difficulties have been established in multiple studies as barriers to radiotherapy for both definitive and palliative management.^15-18 Travel for radiotherapy was much less frequently reported as a barrier among respondents with onsite radiation oncology departments compared with those without onsite radiation departments (28% vs 71%, respectively; P < .001).

It is therefore possible that expansion of VHA radiation oncology services, allowing for provision of onsite radiotherapy at more VHA facilities, would reduce travel burden. Increasing travel accommodations for patients and provision of patient lodging on hospital campuses, which is already offered at some VHA medical centers (ie, Fisher House Foundation), could also help attenuate this barrier.

Multidisciplinary Tumor Boards

Our study demonstrates that centers with onsite radiation departments more frequently hold multidisciplinary tumor boards compared with centers without radiation departments (31% vs 3%, respectively; P = .01). Multidisciplinary tumor boards allow subspecialties to meet regularly to communicate about patient care and can help mitigate barriers related to communication and education of the referring health care practitioners.

As cases are discussed in multidisciplinary tumor boards, health care practitioners have the opportunity to make recommendations and provide education on potential benefits and/or downsides of treatments offered by their respective specialties. Several studies have demonstrated that cases discussed at multidisciplinary tumor boards are more likely to be referred for radiation therapy.^19-21 Furthermore, multidisciplinary tumor boards have been associated with improved treatment outcomes.²²

Conclusions

In this consensus statement the VHA Palliative Radiotherapy Taskforce recommends the optimization of use of radiotherapy within the VHA. Radiation oncology services should be maintained where present in the VHA, with consideration for expansion of services to additional facilities. Telehealth should be used to expedite consults and treatment. Hypofractionation should be used, when appropriate, to ease travel burden. Options for transportation services and onsite housing, or hospitalization, should be understood by practitioners and offered to patients to mitigate barriers related to travel.

Nasopharyngeal carcinoma (NPC) differs from other head and neck (H&N) cancers in its epidemiology and treatment. Unlike other H&N cancers, NPC has a distinct geographical distribution with a much higher incidence in endemic areas, such as southern China, than in areas where it is relatively uncommon, such as the United States.¹ The etiology of NPC varies based on the geographical distribution, with Epstein-Barr virus (EBV) thought to be the primary etiologic agent in endemic areas. On the other hand, in North America 2 additional subsets of NPC have been identified: human papillomavirus (HPV)–positive/EBV-negative and HPV-negative/EBV-negative.^2,3 NPC arises from the epithelial lining of the nasopharynx, often in the fossa of Rosenmuller, and is the most seen tumor in the nasopharynx.⁴ NPC is less surgically accessible than other H&N cancers, and surgery to the nasopharynx poses more risks given the proximity of critical surrounding structures. NPC is radiosensitive, and therefore radiotherapy (RT), in combination with chemotherapy for locally advanced tumors, has become the mainstay of treatment for nonmetastatic NPC.⁴

NPC often presents with an asymptomatic neck mass or with symptoms of epistaxis, nasal obstruction, and otitis media.⁵ Advanced cases of NPC can present with direct extension into the skull base, paranasal sinuses, and orbit, as well as involvement of cranial nerves. Radiation planning for tumors of the nasopharynx is complicated by the need to deliver an adequate dose to the tumor while limiting dose and toxicity to nearby critical structures such as the brainstem, optic chiasm, eyes, spinal cord (SC), temporal lobes, and cochleae. Achieving an adequate dose to nasopharyngeal primary tumors is especially complicated for T4 tumors invading the skull base with intracranial extension, in direct contact with these critical structures (Table 1).

Case Presentation

A 34-year-old male patient with no previous medical history presented to the emergency department with worsening diplopia, nasal obstruction, facial pain, and neck stiffness. The patient reported a 3 pack-year smoking history with recent smoking cessation. His physical examination was notable for a right abducens nerve palsy and an ulcerated nasopharyngeal mass on endoscopy.

Computed tomography (CT) scan revealed a 7-cm mass in the nasopharynx, eroding through the skull base with destruction and replacement of the clivus by tumor. Also noted was erosion of the petrous apices, carotid canals, sella turcica, dens, and the bilateral occipital condyles. There was intracranial extension with replacement of portions of the cavernous sinuses as well as mass effect on the prepontine cistern. Additional brain imaging studies, including magnetic resonance imaging (MRI) and positron emission tomography (PET) scans, were obtained for completion of the staging workup. The MRI correlated with the findings noted on CT and demonstrated involvement of Meckel cave, foramen ovale, foramen rotundum, Dorello canal, and the hypoglossal canals. No cervical lymphadenopathy or distant metastases were noted on imaging. Pathology from biopsy revealed poorly differentiated squamous cell carcinoma, EBV-negative, strongly p16-positive, HPV-16 positive, and P53-negative.

RT planning was complicated by the tumor’s contact with the brainstem and upper cervical SC, as well as proximity of the tumor to the optic apparatus. The patient underwent 2 replanning CT scans at 26 Gy and 44 Gy to evaluate for tumor shrinkage. These CT scans demonstrated shrinkage of the tumor away from critical neural structures, allowing the treatment volume to be reduced away from these structures in order to achieve required dose tolerances (brainstem < 54 Gy, optic nerves and chiasm < 50 Gy, SC < 45 Gy for this case). The replanning CT scan at 44 Gy, 5 weeks after treatment initiation, demonstrated that dramatic tumor shrinkage had occurred early in treatment, with separation of the remaining tumor from the area of the SC and brainstem with which it was initially in contact (Figure 1). This improvement allowed for shrinkage of the high-dose radiation field away from these critical neural structures.

Discussion

RT for NPC is complicated by the proximity of these tumors to critical surrounding neural structures. It is challenging to achieve the required dose constraints to surrounding neural tissues while delivering the usual 70-Gy dose to the gross tumor, especially when the tumor comes into direct contact with these structures.

This case provides an example of response-adapted RT using imaging during treatment to shrink the high-dose target as the tumor shrinks away from critical surrounding structures.⁷ This strategy permits delivery of the maximum dose to the tumor while minimizing radiation dose, and therefore risk of toxicity, to normal surrounding structures. While it is typical to deliver 70 Gy to the full extent of tumor involvement for H&N tumors, this was not possible in this case as the tumor was in contact with the brainstem and upper cervical SC. Delivering the full 70 Gy to these areas of tumor would have placed this patient at substantial risk of brainstem and/or SC toxicity. This report demonstrates that response-adapted RT with shrinking fields can allow for tumor control while avoiding toxicity to critical neural structures for cases of locally advanced NPC in which tumor is abutting these structures.

Bony regeneration of the skull base following RT has been reported in the literature, but in limited reviews. Early reports used plain radiography to follow changes. Unger and colleagues demonstrated the regeneration of bone using skull radiographs 4 to 6 months after completion of RT for NPC.⁸ More recent literature details the ability of bone to regenerate after RT based on CT findings. Fang and colleagues reported on 90 cases of NPC with skull base destruction, with 63% having bony regeneration on posttreatment CT.⁹ Most of the patients in Fang’s report had bony regeneration within 1 year of treatment, and in general, bony regeneration became more evident on imaging with longer follow-up. Of note, local control was significantly greater in patients with regeneration vs persistent destruction (77% vs 21%, P < .001). On multivariate analysis, complete tumor response was significantly associated with bony regeneration; other factors such as age, sex, radiation dose, and chemotherapy were not significantly associated with the likelihood of bony regeneration.

Our report details a nasopharyngeal tumor that destroyed the skull base with no intact bony barrier. In such cases, concern arises regarding craniospinal instability with tumor regression if there is not simultaneous bone regeneration. Tumor invasion of the skull base and C1-2 vertebral bodies and complications from treatment of such tumor extent can lead to symptoms of craniospinal instability, including pain, difficulty with neck range of motion, and loss of strength and sensation in the upper and lower extremities.¹⁰ A case report of a woman treated with chemoradiation for a plasmacytoma of the skull base detailed her posttreatment presentation with quadriparesis resulting from craniospinal instability after tumor regression.¹¹ Such instability is generally treated surgically, and during this woman’s surgery, there was an injury to the right vertebral artery, although this did not cause any additional neurologic deficits.

Conclusions

There is a paucity of literature on bony regeneration in patients with skull base destruction from advanced NPC, and in particular, the ability of skull base regeneration to occur during treatment simultaneous with tumor regression. Our patient had HPV-positive/EBV-negative NPC, but it is unclear how this subtype affected his prognosis. Factors such as tumor histology, radiosensitivity with rapid tumor regression, and young age may have all contributed to the rapidity of bone regeneration in our patient. This case report demonstrates that an impressive tumor response to chemoradiation with simultaneous bony regeneration is possible among patients presenting with tumor destruction of the skull base, precluding the need for neurosurgical intervention.

Nasopharyngeal carcinoma (NPC) differs from other head and neck (H&N) cancers in its epidemiology and treatment. Unlike other H&N cancers, NPC has a distinct geographical distribution with a much higher incidence in endemic areas, such as southern China, than in areas where it is relatively uncommon, such as the United States.¹ The etiology of NPC varies based on the geographical distribution, with Epstein-Barr virus (EBV) thought to be the primary etiologic agent in endemic areas. On the other hand, in North America 2 additional subsets of NPC have been identified: human papillomavirus (HPV)–positive/EBV-negative and HPV-negative/EBV-negative.^2,3 NPC arises from the epithelial lining of the nasopharynx, often in the fossa of Rosenmuller, and is the most seen tumor in the nasopharynx.⁴ NPC is less surgically accessible than other H&N cancers, and surgery to the nasopharynx poses more risks given the proximity of critical surrounding structures. NPC is radiosensitive, and therefore radiotherapy (RT), in combination with chemotherapy for locally advanced tumors, has become the mainstay of treatment for nonmetastatic NPC.⁴

NPC often presents with an asymptomatic neck mass or with symptoms of epistaxis, nasal obstruction, and otitis media.⁵ Advanced cases of NPC can present with direct extension into the skull base, paranasal sinuses, and orbit, as well as involvement of cranial nerves. Radiation planning for tumors of the nasopharynx is complicated by the need to deliver an adequate dose to the tumor while limiting dose and toxicity to nearby critical structures such as the brainstem, optic chiasm, eyes, spinal cord (SC), temporal lobes, and cochleae. Achieving an adequate dose to nasopharyngeal primary tumors is especially complicated for T4 tumors invading the skull base with intracranial extension, in direct contact with these critical structures (Table 1).

Case Presentation

A 34-year-old male patient with no previous medical history presented to the emergency department with worsening diplopia, nasal obstruction, facial pain, and neck stiffness. The patient reported a 3 pack-year smoking history with recent smoking cessation. His physical examination was notable for a right abducens nerve palsy and an ulcerated nasopharyngeal mass on endoscopy.

Computed tomography (CT) scan revealed a 7-cm mass in the nasopharynx, eroding through the skull base with destruction and replacement of the clivus by tumor. Also noted was erosion of the petrous apices, carotid canals, sella turcica, dens, and the bilateral occipital condyles. There was intracranial extension with replacement of portions of the cavernous sinuses as well as mass effect on the prepontine cistern. Additional brain imaging studies, including magnetic resonance imaging (MRI) and positron emission tomography (PET) scans, were obtained for completion of the staging workup. The MRI correlated with the findings noted on CT and demonstrated involvement of Meckel cave, foramen ovale, foramen rotundum, Dorello canal, and the hypoglossal canals. No cervical lymphadenopathy or distant metastases were noted on imaging. Pathology from biopsy revealed poorly differentiated squamous cell carcinoma, EBV-negative, strongly p16-positive, HPV-16 positive, and P53-negative.

RT planning was complicated by the tumor’s contact with the brainstem and upper cervical SC, as well as proximity of the tumor to the optic apparatus. The patient underwent 2 replanning CT scans at 26 Gy and 44 Gy to evaluate for tumor shrinkage. These CT scans demonstrated shrinkage of the tumor away from critical neural structures, allowing the treatment volume to be reduced away from these structures in order to achieve required dose tolerances (brainstem < 54 Gy, optic nerves and chiasm < 50 Gy, SC < 45 Gy for this case). The replanning CT scan at 44 Gy, 5 weeks after treatment initiation, demonstrated that dramatic tumor shrinkage had occurred early in treatment, with separation of the remaining tumor from the area of the SC and brainstem with which it was initially in contact (Figure 1). This improvement allowed for shrinkage of the high-dose radiation field away from these critical neural structures.

Discussion

RT for NPC is complicated by the proximity of these tumors to critical surrounding neural structures. It is challenging to achieve the required dose constraints to surrounding neural tissues while delivering the usual 70-Gy dose to the gross tumor, especially when the tumor comes into direct contact with these structures.

This case provides an example of response-adapted RT using imaging during treatment to shrink the high-dose target as the tumor shrinks away from critical surrounding structures.⁷ This strategy permits delivery of the maximum dose to the tumor while minimizing radiation dose, and therefore risk of toxicity, to normal surrounding structures. While it is typical to deliver 70 Gy to the full extent of tumor involvement for H&N tumors, this was not possible in this case as the tumor was in contact with the brainstem and upper cervical SC. Delivering the full 70 Gy to these areas of tumor would have placed this patient at substantial risk of brainstem and/or SC toxicity. This report demonstrates that response-adapted RT with shrinking fields can allow for tumor control while avoiding toxicity to critical neural structures for cases of locally advanced NPC in which tumor is abutting these structures.

Bony regeneration of the skull base following RT has been reported in the literature, but in limited reviews. Early reports used plain radiography to follow changes. Unger and colleagues demonstrated the regeneration of bone using skull radiographs 4 to 6 months after completion of RT for NPC.⁸ More recent literature details the ability of bone to regenerate after RT based on CT findings. Fang and colleagues reported on 90 cases of NPC with skull base destruction, with 63% having bony regeneration on posttreatment CT.⁹ Most of the patients in Fang’s report had bony regeneration within 1 year of treatment, and in general, bony regeneration became more evident on imaging with longer follow-up. Of note, local control was significantly greater in patients with regeneration vs persistent destruction (77% vs 21%, P < .001). On multivariate analysis, complete tumor response was significantly associated with bony regeneration; other factors such as age, sex, radiation dose, and chemotherapy were not significantly associated with the likelihood of bony regeneration.

Our report details a nasopharyngeal tumor that destroyed the skull base with no intact bony barrier. In such cases, concern arises regarding craniospinal instability with tumor regression if there is not simultaneous bone regeneration. Tumor invasion of the skull base and C1-2 vertebral bodies and complications from treatment of such tumor extent can lead to symptoms of craniospinal instability, including pain, difficulty with neck range of motion, and loss of strength and sensation in the upper and lower extremities.¹⁰ A case report of a woman treated with chemoradiation for a plasmacytoma of the skull base detailed her posttreatment presentation with quadriparesis resulting from craniospinal instability after tumor regression.¹¹ Such instability is generally treated surgically, and during this woman’s surgery, there was an injury to the right vertebral artery, although this did not cause any additional neurologic deficits.

Conclusions

There is a paucity of literature on bony regeneration in patients with skull base destruction from advanced NPC, and in particular, the ability of skull base regeneration to occur during treatment simultaneous with tumor regression. Our patient had HPV-positive/EBV-negative NPC, but it is unclear how this subtype affected his prognosis. Factors such as tumor histology, radiosensitivity with rapid tumor regression, and young age may have all contributed to the rapidity of bone regeneration in our patient. This case report demonstrates that an impressive tumor response to chemoradiation with simultaneous bony regeneration is possible among patients presenting with tumor destruction of the skull base, precluding the need for neurosurgical intervention.

Nasopharyngeal carcinoma (NPC) differs from other head and neck (H&N) cancers in its epidemiology and treatment. Unlike other H&N cancers, NPC has a distinct geographical distribution with a much higher incidence in endemic areas, such as southern China, than in areas where it is relatively uncommon, such as the United States.¹ The etiology of NPC varies based on the geographical distribution, with Epstein-Barr virus (EBV) thought to be the primary etiologic agent in endemic areas. On the other hand, in North America 2 additional subsets of NPC have been identified: human papillomavirus (HPV)–positive/EBV-negative and HPV-negative/EBV-negative.^2,3 NPC arises from the epithelial lining of the nasopharynx, often in the fossa of Rosenmuller, and is the most seen tumor in the nasopharynx.⁴ NPC is less surgically accessible than other H&N cancers, and surgery to the nasopharynx poses more risks given the proximity of critical surrounding structures. NPC is radiosensitive, and therefore radiotherapy (RT), in combination with chemotherapy for locally advanced tumors, has become the mainstay of treatment for nonmetastatic NPC.⁴

NPC often presents with an asymptomatic neck mass or with symptoms of epistaxis, nasal obstruction, and otitis media.⁵ Advanced cases of NPC can present with direct extension into the skull base, paranasal sinuses, and orbit, as well as involvement of cranial nerves. Radiation planning for tumors of the nasopharynx is complicated by the need to deliver an adequate dose to the tumor while limiting dose and toxicity to nearby critical structures such as the brainstem, optic chiasm, eyes, spinal cord (SC), temporal lobes, and cochleae. Achieving an adequate dose to nasopharyngeal primary tumors is especially complicated for T4 tumors invading the skull base with intracranial extension, in direct contact with these critical structures (Table 1).

Case Presentation

A 34-year-old male patient with no previous medical history presented to the emergency department with worsening diplopia, nasal obstruction, facial pain, and neck stiffness. The patient reported a 3 pack-year smoking history with recent smoking cessation. His physical examination was notable for a right abducens nerve palsy and an ulcerated nasopharyngeal mass on endoscopy.

Computed tomography (CT) scan revealed a 7-cm mass in the nasopharynx, eroding through the skull base with destruction and replacement of the clivus by tumor. Also noted was erosion of the petrous apices, carotid canals, sella turcica, dens, and the bilateral occipital condyles. There was intracranial extension with replacement of portions of the cavernous sinuses as well as mass effect on the prepontine cistern. Additional brain imaging studies, including magnetic resonance imaging (MRI) and positron emission tomography (PET) scans, were obtained for completion of the staging workup. The MRI correlated with the findings noted on CT and demonstrated involvement of Meckel cave, foramen ovale, foramen rotundum, Dorello canal, and the hypoglossal canals. No cervical lymphadenopathy or distant metastases were noted on imaging. Pathology from biopsy revealed poorly differentiated squamous cell carcinoma, EBV-negative, strongly p16-positive, HPV-16 positive, and P53-negative.

RT planning was complicated by the tumor’s contact with the brainstem and upper cervical SC, as well as proximity of the tumor to the optic apparatus. The patient underwent 2 replanning CT scans at 26 Gy and 44 Gy to evaluate for tumor shrinkage. These CT scans demonstrated shrinkage of the tumor away from critical neural structures, allowing the treatment volume to be reduced away from these structures in order to achieve required dose tolerances (brainstem < 54 Gy, optic nerves and chiasm < 50 Gy, SC < 45 Gy for this case). The replanning CT scan at 44 Gy, 5 weeks after treatment initiation, demonstrated that dramatic tumor shrinkage had occurred early in treatment, with separation of the remaining tumor from the area of the SC and brainstem with which it was initially in contact (Figure 1). This improvement allowed for shrinkage of the high-dose radiation field away from these critical neural structures.

Discussion

RT for NPC is complicated by the proximity of these tumors to critical surrounding neural structures. It is challenging to achieve the required dose constraints to surrounding neural tissues while delivering the usual 70-Gy dose to the gross tumor, especially when the tumor comes into direct contact with these structures.

This case provides an example of response-adapted RT using imaging during treatment to shrink the high-dose target as the tumor shrinks away from critical surrounding structures.⁷ This strategy permits delivery of the maximum dose to the tumor while minimizing radiation dose, and therefore risk of toxicity, to normal surrounding structures. While it is typical to deliver 70 Gy to the full extent of tumor involvement for H&N tumors, this was not possible in this case as the tumor was in contact with the brainstem and upper cervical SC. Delivering the full 70 Gy to these areas of tumor would have placed this patient at substantial risk of brainstem and/or SC toxicity. This report demonstrates that response-adapted RT with shrinking fields can allow for tumor control while avoiding toxicity to critical neural structures for cases of locally advanced NPC in which tumor is abutting these structures.

Bony regeneration of the skull base following RT has been reported in the literature, but in limited reviews. Early reports used plain radiography to follow changes. Unger and colleagues demonstrated the regeneration of bone using skull radiographs 4 to 6 months after completion of RT for NPC.⁸ More recent literature details the ability of bone to regenerate after RT based on CT findings. Fang and colleagues reported on 90 cases of NPC with skull base destruction, with 63% having bony regeneration on posttreatment CT.⁹ Most of the patients in Fang’s report had bony regeneration within 1 year of treatment, and in general, bony regeneration became more evident on imaging with longer follow-up. Of note, local control was significantly greater in patients with regeneration vs persistent destruction (77% vs 21%, P < .001). On multivariate analysis, complete tumor response was significantly associated with bony regeneration; other factors such as age, sex, radiation dose, and chemotherapy were not significantly associated with the likelihood of bony regeneration.

Our report details a nasopharyngeal tumor that destroyed the skull base with no intact bony barrier. In such cases, concern arises regarding craniospinal instability with tumor regression if there is not simultaneous bone regeneration. Tumor invasion of the skull base and C1-2 vertebral bodies and complications from treatment of such tumor extent can lead to symptoms of craniospinal instability, including pain, difficulty with neck range of motion, and loss of strength and sensation in the upper and lower extremities.¹⁰ A case report of a woman treated with chemoradiation for a plasmacytoma of the skull base detailed her posttreatment presentation with quadriparesis resulting from craniospinal instability after tumor regression.¹¹ Such instability is generally treated surgically, and during this woman’s surgery, there was an injury to the right vertebral artery, although this did not cause any additional neurologic deficits.

Conclusions

There is a paucity of literature on bony regeneration in patients with skull base destruction from advanced NPC, and in particular, the ability of skull base regeneration to occur during treatment simultaneous with tumor regression. Our patient had HPV-positive/EBV-negative NPC, but it is unclear how this subtype affected his prognosis. Factors such as tumor histology, radiosensitivity with rapid tumor regression, and young age may have all contributed to the rapidity of bone regeneration in our patient. This case report demonstrates that an impressive tumor response to chemoradiation with simultaneous bony regeneration is possible among patients presenting with tumor destruction of the skull base, precluding the need for neurosurgical intervention.

Lung cancer is the leading cause of cancer mortality both in the US and worldwide.¹ Many patients diagnosed with lung cancer present with advanced disease with thoracic symptoms such as cough, hemoptysis, dyspnea, and chest pain.^2-4 Palliative radiotherapy is routinely used in patients with locally advanced and metastatic lung cancer with the goal of relieving these symptoms and improving quality of life. Guidelines published by the American Society for Radiation Oncology (ASTRO) in 2011, and updated in 2018, provide recommendations on palliation of lung cancer with external beam radiotherapy (EBRT) and clarify the roles of concurrent chemotherapy and endobronchial brachytherapy (EBB) for palliation.^5,6

After prostate cancer, lung cancer is the second most frequently diagnosed cancer in the Veterans Health Administration (VHA).⁷ The VHA consists of 172 medical centers and is the largest integrated health care system in the US. At the time of this study, 40 of these centers had onsite radiation facilities. The VHA Palliative Radiation Taskforce has conducted a series of surveys to evaluate use of palliative radiotherapy in the VHA, determine VHA practice concordance with ASTRO and American College of Radiology (ACR) guidelines, and direct educational efforts towards addressing gaps in knowledge. These efforts are directed at ensuring best practices throughout this large and heterogeneous healthcare system. In 2016 a survey was conducted to evaluate concordance of VHA radiation oncologist (RO) practice with the 2011 ASTRO guidelines on palliative thoracic radiotherapy for non-small cell lung cancer (NSCLC).

Methods

A survey instrument was generated by VHA National Palliative Radiotherapy Taskforce members. It was reviewed and approved for use by the VHA Patient Care Services office. In May of 2016, the online survey was sent to the 88 VHA ROs practicing at the 40 sites with onsite radiation facilities. The survey aimed to determine patterns of practice for palliation of thoracic symptoms secondary to lung cancer.

Demographic information obtained included years in practice, employment status, academic appointment, board certification, and familiarity with ASTRO lung cancer guidelines. Two clinical scenarios were presented to glean opinions on dose/fractionation schemes preferred, use of concurrent chemotherapy, and use of EBB and/or yttrium aluminum garnet (YAG) laser technology. Survey questions also assessed use of EBRT for palliation of hemoptysis, chest wall pain, and/or stridor as well as use of stereotactic body radiotherapy (SBRT) for palliation.

Survey results were assessed for concordance with published ASTRO guidelines. χ² tests were run to test for associations between demographic factors such as academic appointment, years of practice, full time vs part time employment, and familiarity with ASTRO palliative lung cancer guidelines, with use of EBRT for palliation, dose and fractionation preference, use of concurrent chemotherapy, and strategy for management of endobronchial lesions.

Results

Of the 88 physicians surveyed, 54 responded for a response rate of 61%. Respondents represented 37 of the 40 (93%) VHA radiation oncology departments (Table 1). Among respondents, most were board certified (96%), held academic appointments (91%), and were full-time employees (85%). Forty-four percent of respondents were in practice for > 20 years, 19% for 11 to 20 years, 20% for 6 to 10 years, and 17% for < 6 years. A majority reported familiarity with the ASTRO guidelines (64%), while just 11% reported no familiarity with the guidelines.

When asked about use of SBRT for palliation of hemoptysis, stridor, and/or chest pain, the majority (87%) preferred conventional EBRT. Of the 13% who reported use of SBRT, most (11%) performed it onsite, with 2% of respondents referring offsite to non-VHA centers for the service. When asked about use of EBB for palliation, only 2% reported use of that procedure at their facilities, while 26% reported referral to non-VHA facilities for EBB. The remaining 72% of respondents favor use of conventional EBRT.

Respondents were presented with a case of a male patient aged 70 years who smoked and had widely metastatic NSCLC, a life expectancy of about 3 months, and 10/10 chest wall pain from direct tumor invasion. All respondents recommended palliative radiotherapy. The preferred fractionation was 20 Gray (Gy) in 5 fractions, which was recommended by 69% of respondents. The remainder recommended 30 Gy in 10 fractions (22%) or a single fraction of 10 Gy (9%). No respondent recommended the longer fractionation options of 60 Gy in 30 fractions, 45 Gy in 15 fractions, or 40 Gy in 20 fractions. The majority (98%) did not recommend concurrent chemotherapy.

When the above case was modified for an endobronchial lesion requiring palliation with associated lung collapse, rather than chest wall invasion, 20 respondents (38%) reported they would refer for EBB, and 20 respondents reported they would refer for YAG laser. As > 1 answer could be selected for this question, there were 12 respondents who selected both EBB and YAG laser; 8 selected only EBB, and 8 selected only YAG laser. Many respondents added comments about treating with EBRT, which had not been presented as an answer choice. Nearly half of respondents (49%) were amenable to referral for the use of EBB or YAG laser for lung reexpansion prior to radiotherapy. Three respondents mentioned referral for an endobronchial stent prior to palliative radiotherapy to address this question.

Discussion

This survey was conducted to evaluate concordance of management of metastatic lung cancer in the VHA with ASTRO guidelines. The relationship between respondents’ familiarity with the guidelines and responses also was evaluated to determine the impact such guidelines have on decision-making. The ASTRO guidelines for palliative thoracic radiation make recommendations regarding 3 issues: (1) radiation doses and fractionations for palliation; (2) the role of EBB; and (3) the use of concurrent chemotherapy.^5,6

Radiation Dose and Fractionation for Palliation

A variety of dose/fractionation schemes are considered appropriate in the ASTRO guideline statement, including more prolonged courses such as 30 Gy/10 fractions as well as more hypofractionated regimens (ie, 20 Gy/5 fractions, 17 Gy/2 fractions, and a single fraction of 10 Gy). Higher dose regimens, such as 30 Gy/10 fractions, have been associated with prolonged survival, as well as increased toxicities such as radiation esophagitis.⁸ Therefore, the guidelines support use of 30 Gy/10 fractions for patients with good performance status while encouraging use of more hypofractionated regimens for patients with poor performance status. In considering more hypofractionated regimens, one must consider the possibility of adverse effects that can be associated with higher dose per fraction. For instance, 17 Gy/2 fractions has been associated with myelopathy; therefore it should be used with caution and careful treatment planning.⁹

For the survey case example (a male aged 70 years with a 3-month life expectancy who required palliation for chest wall pain), all respondents selected hypofractionated regimens; with no respondent selected the more prolonged fractionations of 60 Gy/30 fractions, 45 Gy/15 fractions, or 40 Gy/20 fractions. These more prolonged fractionations are not endorsed by the guidelines in general, and particularly not for a patient with poor life expectancy. All responses for this case selected by survey respondents are considered appropriate per the consensus guideline statement.

Role of Concurrent Chemotherapy

The ASTRO guidelines do not support use of concurrent chemotherapy for palliation of stage IV NSCLC.^5,6 The 2018 updated guidelines established a role for concurrent chemotherapy for patients with stage III NSCLC with good performance status and life expectancy of > 3 months. This updated recommendation is based on data from 2 randomized trials demonstrating improvement in overall survival with the addition of chemotherapy for patients with stage III NSCLC undergoing palliative radiotherapy.^10-12

These newer studies are in contrast to an older randomized study by Ball and colleagues that demonstrated greater toxicity from concurrent chemotherapy, with no improvement in outcomes such as palliation of symptoms, overall survival, or progression free survival.¹³ In contrast to the newer studies that included only patients with stage III NSCLC, about half of the patients in the Ball and colleagues study had known metastatic disease.^10-13 Of note, staging for metastatic disease was not carried out routinely, so it is possible that a greater proportion of patients had metastatic disease that would have been seen on imaging. In concordance with the guidelines, 98% of the survey respondents did not recommend concurrent chemotherapy for palliation of intrathoracic symptom; only 1 respondent recommended use of chemotherapy for palliation.

Role of Endobronchial Brachytherapy

EBB involves implantation of radioactive sources for treatment of endobronchial lesions causing obstructive symptoms.¹⁴ Given the lack of randomized data that demonstrate a benefit of EBB over EBRT, the ASTRO guidelines do not endorse routine use of EBB for initial palliative management.^15,16 The ASTRO guidelines reference a Cochrane Review of 13 trials that concluded that EBRT alone is superior to EBB alone for initial palliation of symptoms from endobronchial NSCLC.¹⁷

Of respondents surveyed, only 1 facility offered onsite EBB. The majority of respondents (72%) preferred the use of conventional EBRT techniques, while 26% refer to non-VHA centers for EBB. Lack of incorporation of EBB into routine VHA practice likely is a reflection of the unclear role of this technology based on the available literature and ASTRO guidelines. In the setting of a right lower lung collapse, more respondents (49%) would consider use of EBB or YAG laser technology for lung reexpansion prior to EBRT.

The ASTRO guidelines recommend that initial EBB in conjunction with EBRT be considered based on randomized data demonstrating significant improvement in lung reexpansion and in patient reported dyspnea with addition of EBB to EBRT over EBRT alone.¹⁸ However, the guidelines do not mandate the use of EBB in this situation. It is possible that targeted education regarding the role of EBB would improve knowledge of the potential benefit in the setting of lung collapse and increase the percentage of VHA ROs who would recommend this procedure.

Limitations

The study is limited by lack of generalizability of these findings to all ROs in the country. It is also possible that physician responses do not represent practice patterns with complete accuracy. The use of EBB varied among practitioners. Further study of this technology is necessary to clarify its role in the management of endobronchial obstructive symptoms and to determine whether efforts should be made to increase access to EBB within the VHA.

Conclusions

Most of the ROs who responded to our survey were cognizant and compliant with current ASTRO guidelines on management of lung cancer. Furthermore, familiarity with ASTRO guidelines and management choices were not associated with the respondents’ years in practice, academic appointment, full-time vs part-time status, or familiarity with ASTRO guidelines. This study is a nationwide survey of ROs in the VHA system that reflects the radiation-related care received by veterans with metastatic lung cancer. Responses were obtained from 93% of the 40 radiation oncology centers, so it is likely that the survey accurately represents the decision-making process at the majority of centers. It is possible that those who did not respond to the survey do not treat thoracic cases.

Lung cancer is the leading cause of cancer mortality both in the US and worldwide.¹ Many patients diagnosed with lung cancer present with advanced disease with thoracic symptoms such as cough, hemoptysis, dyspnea, and chest pain.^2-4 Palliative radiotherapy is routinely used in patients with locally advanced and metastatic lung cancer with the goal of relieving these symptoms and improving quality of life. Guidelines published by the American Society for Radiation Oncology (ASTRO) in 2011, and updated in 2018, provide recommendations on palliation of lung cancer with external beam radiotherapy (EBRT) and clarify the roles of concurrent chemotherapy and endobronchial brachytherapy (EBB) for palliation.^5,6

After prostate cancer, lung cancer is the second most frequently diagnosed cancer in the Veterans Health Administration (VHA).⁷ The VHA consists of 172 medical centers and is the largest integrated health care system in the US. At the time of this study, 40 of these centers had onsite radiation facilities. The VHA Palliative Radiation Taskforce has conducted a series of surveys to evaluate use of palliative radiotherapy in the VHA, determine VHA practice concordance with ASTRO and American College of Radiology (ACR) guidelines, and direct educational efforts towards addressing gaps in knowledge. These efforts are directed at ensuring best practices throughout this large and heterogeneous healthcare system. In 2016 a survey was conducted to evaluate concordance of VHA radiation oncologist (RO) practice with the 2011 ASTRO guidelines on palliative thoracic radiotherapy for non-small cell lung cancer (NSCLC).

Methods

A survey instrument was generated by VHA National Palliative Radiotherapy Taskforce members. It was reviewed and approved for use by the VHA Patient Care Services office. In May of 2016, the online survey was sent to the 88 VHA ROs practicing at the 40 sites with onsite radiation facilities. The survey aimed to determine patterns of practice for palliation of thoracic symptoms secondary to lung cancer.

Demographic information obtained included years in practice, employment status, academic appointment, board certification, and familiarity with ASTRO lung cancer guidelines. Two clinical scenarios were presented to glean opinions on dose/fractionation schemes preferred, use of concurrent chemotherapy, and use of EBB and/or yttrium aluminum garnet (YAG) laser technology. Survey questions also assessed use of EBRT for palliation of hemoptysis, chest wall pain, and/or stridor as well as use of stereotactic body radiotherapy (SBRT) for palliation.

Survey results were assessed for concordance with published ASTRO guidelines. χ² tests were run to test for associations between demographic factors such as academic appointment, years of practice, full time vs part time employment, and familiarity with ASTRO palliative lung cancer guidelines, with use of EBRT for palliation, dose and fractionation preference, use of concurrent chemotherapy, and strategy for management of endobronchial lesions.

Results

Of the 88 physicians surveyed, 54 responded for a response rate of 61%. Respondents represented 37 of the 40 (93%) VHA radiation oncology departments (Table 1). Among respondents, most were board certified (96%), held academic appointments (91%), and were full-time employees (85%). Forty-four percent of respondents were in practice for > 20 years, 19% for 11 to 20 years, 20% for 6 to 10 years, and 17% for < 6 years. A majority reported familiarity with the ASTRO guidelines (64%), while just 11% reported no familiarity with the guidelines.

When asked about use of SBRT for palliation of hemoptysis, stridor, and/or chest pain, the majority (87%) preferred conventional EBRT. Of the 13% who reported use of SBRT, most (11%) performed it onsite, with 2% of respondents referring offsite to non-VHA centers for the service. When asked about use of EBB for palliation, only 2% reported use of that procedure at their facilities, while 26% reported referral to non-VHA facilities for EBB. The remaining 72% of respondents favor use of conventional EBRT.

Respondents were presented with a case of a male patient aged 70 years who smoked and had widely metastatic NSCLC, a life expectancy of about 3 months, and 10/10 chest wall pain from direct tumor invasion. All respondents recommended palliative radiotherapy. The preferred fractionation was 20 Gray (Gy) in 5 fractions, which was recommended by 69% of respondents. The remainder recommended 30 Gy in 10 fractions (22%) or a single fraction of 10 Gy (9%). No respondent recommended the longer fractionation options of 60 Gy in 30 fractions, 45 Gy in 15 fractions, or 40 Gy in 20 fractions. The majority (98%) did not recommend concurrent chemotherapy.

When the above case was modified for an endobronchial lesion requiring palliation with associated lung collapse, rather than chest wall invasion, 20 respondents (38%) reported they would refer for EBB, and 20 respondents reported they would refer for YAG laser. As > 1 answer could be selected for this question, there were 12 respondents who selected both EBB and YAG laser; 8 selected only EBB, and 8 selected only YAG laser. Many respondents added comments about treating with EBRT, which had not been presented as an answer choice. Nearly half of respondents (49%) were amenable to referral for the use of EBB or YAG laser for lung reexpansion prior to radiotherapy. Three respondents mentioned referral for an endobronchial stent prior to palliative radiotherapy to address this question.

Discussion

This survey was conducted to evaluate concordance of management of metastatic lung cancer in the VHA with ASTRO guidelines. The relationship between respondents’ familiarity with the guidelines and responses also was evaluated to determine the impact such guidelines have on decision-making. The ASTRO guidelines for palliative thoracic radiation make recommendations regarding 3 issues: (1) radiation doses and fractionations for palliation; (2) the role of EBB; and (3) the use of concurrent chemotherapy.^5,6

Radiation Dose and Fractionation for Palliation

A variety of dose/fractionation schemes are considered appropriate in the ASTRO guideline statement, including more prolonged courses such as 30 Gy/10 fractions as well as more hypofractionated regimens (ie, 20 Gy/5 fractions, 17 Gy/2 fractions, and a single fraction of 10 Gy). Higher dose regimens, such as 30 Gy/10 fractions, have been associated with prolonged survival, as well as increased toxicities such as radiation esophagitis.⁸ Therefore, the guidelines support use of 30 Gy/10 fractions for patients with good performance status while encouraging use of more hypofractionated regimens for patients with poor performance status. In considering more hypofractionated regimens, one must consider the possibility of adverse effects that can be associated with higher dose per fraction. For instance, 17 Gy/2 fractions has been associated with myelopathy; therefore it should be used with caution and careful treatment planning.⁹

For the survey case example (a male aged 70 years with a 3-month life expectancy who required palliation for chest wall pain), all respondents selected hypofractionated regimens; with no respondent selected the more prolonged fractionations of 60 Gy/30 fractions, 45 Gy/15 fractions, or 40 Gy/20 fractions. These more prolonged fractionations are not endorsed by the guidelines in general, and particularly not for a patient with poor life expectancy. All responses for this case selected by survey respondents are considered appropriate per the consensus guideline statement.

Role of Concurrent Chemotherapy

The ASTRO guidelines do not support use of concurrent chemotherapy for palliation of stage IV NSCLC.^5,6 The 2018 updated guidelines established a role for concurrent chemotherapy for patients with stage III NSCLC with good performance status and life expectancy of > 3 months. This updated recommendation is based on data from 2 randomized trials demonstrating improvement in overall survival with the addition of chemotherapy for patients with stage III NSCLC undergoing palliative radiotherapy.^10-12

These newer studies are in contrast to an older randomized study by Ball and colleagues that demonstrated greater toxicity from concurrent chemotherapy, with no improvement in outcomes such as palliation of symptoms, overall survival, or progression free survival.¹³ In contrast to the newer studies that included only patients with stage III NSCLC, about half of the patients in the Ball and colleagues study had known metastatic disease.^10-13 Of note, staging for metastatic disease was not carried out routinely, so it is possible that a greater proportion of patients had metastatic disease that would have been seen on imaging. In concordance with the guidelines, 98% of the survey respondents did not recommend concurrent chemotherapy for palliation of intrathoracic symptom; only 1 respondent recommended use of chemotherapy for palliation.

Role of Endobronchial Brachytherapy

EBB involves implantation of radioactive sources for treatment of endobronchial lesions causing obstructive symptoms.¹⁴ Given the lack of randomized data that demonstrate a benefit of EBB over EBRT, the ASTRO guidelines do not endorse routine use of EBB for initial palliative management.^15,16 The ASTRO guidelines reference a Cochrane Review of 13 trials that concluded that EBRT alone is superior to EBB alone for initial palliation of symptoms from endobronchial NSCLC.¹⁷

Of respondents surveyed, only 1 facility offered onsite EBB. The majority of respondents (72%) preferred the use of conventional EBRT techniques, while 26% refer to non-VHA centers for EBB. Lack of incorporation of EBB into routine VHA practice likely is a reflection of the unclear role of this technology based on the available literature and ASTRO guidelines. In the setting of a right lower lung collapse, more respondents (49%) would consider use of EBB or YAG laser technology for lung reexpansion prior to EBRT.

The ASTRO guidelines recommend that initial EBB in conjunction with EBRT be considered based on randomized data demonstrating significant improvement in lung reexpansion and in patient reported dyspnea with addition of EBB to EBRT over EBRT alone.¹⁸ However, the guidelines do not mandate the use of EBB in this situation. It is possible that targeted education regarding the role of EBB would improve knowledge of the potential benefit in the setting of lung collapse and increase the percentage of VHA ROs who would recommend this procedure.

Limitations

The study is limited by lack of generalizability of these findings to all ROs in the country. It is also possible that physician responses do not represent practice patterns with complete accuracy. The use of EBB varied among practitioners. Further study of this technology is necessary to clarify its role in the management of endobronchial obstructive symptoms and to determine whether efforts should be made to increase access to EBB within the VHA.

Conclusions

Most of the ROs who responded to our survey were cognizant and compliant with current ASTRO guidelines on management of lung cancer. Furthermore, familiarity with ASTRO guidelines and management choices were not associated with the respondents’ years in practice, academic appointment, full-time vs part-time status, or familiarity with ASTRO guidelines. This study is a nationwide survey of ROs in the VHA system that reflects the radiation-related care received by veterans with metastatic lung cancer. Responses were obtained from 93% of the 40 radiation oncology centers, so it is likely that the survey accurately represents the decision-making process at the majority of centers. It is possible that those who did not respond to the survey do not treat thoracic cases.

Lung cancer is the leading cause of cancer mortality both in the US and worldwide.¹ Many patients diagnosed with lung cancer present with advanced disease with thoracic symptoms such as cough, hemoptysis, dyspnea, and chest pain.^2-4 Palliative radiotherapy is routinely used in patients with locally advanced and metastatic lung cancer with the goal of relieving these symptoms and improving quality of life. Guidelines published by the American Society for Radiation Oncology (ASTRO) in 2011, and updated in 2018, provide recommendations on palliation of lung cancer with external beam radiotherapy (EBRT) and clarify the roles of concurrent chemotherapy and endobronchial brachytherapy (EBB) for palliation.^5,6

After prostate cancer, lung cancer is the second most frequently diagnosed cancer in the Veterans Health Administration (VHA).⁷ The VHA consists of 172 medical centers and is the largest integrated health care system in the US. At the time of this study, 40 of these centers had onsite radiation facilities. The VHA Palliative Radiation Taskforce has conducted a series of surveys to evaluate use of palliative radiotherapy in the VHA, determine VHA practice concordance with ASTRO and American College of Radiology (ACR) guidelines, and direct educational efforts towards addressing gaps in knowledge. These efforts are directed at ensuring best practices throughout this large and heterogeneous healthcare system. In 2016 a survey was conducted to evaluate concordance of VHA radiation oncologist (RO) practice with the 2011 ASTRO guidelines on palliative thoracic radiotherapy for non-small cell lung cancer (NSCLC).

Methods

A survey instrument was generated by VHA National Palliative Radiotherapy Taskforce members. It was reviewed and approved for use by the VHA Patient Care Services office. In May of 2016, the online survey was sent to the 88 VHA ROs practicing at the 40 sites with onsite radiation facilities. The survey aimed to determine patterns of practice for palliation of thoracic symptoms secondary to lung cancer.

Demographic information obtained included years in practice, employment status, academic appointment, board certification, and familiarity with ASTRO lung cancer guidelines. Two clinical scenarios were presented to glean opinions on dose/fractionation schemes preferred, use of concurrent chemotherapy, and use of EBB and/or yttrium aluminum garnet (YAG) laser technology. Survey questions also assessed use of EBRT for palliation of hemoptysis, chest wall pain, and/or stridor as well as use of stereotactic body radiotherapy (SBRT) for palliation.

Survey results were assessed for concordance with published ASTRO guidelines. χ² tests were run to test for associations between demographic factors such as academic appointment, years of practice, full time vs part time employment, and familiarity with ASTRO palliative lung cancer guidelines, with use of EBRT for palliation, dose and fractionation preference, use of concurrent chemotherapy, and strategy for management of endobronchial lesions.

Results

Of the 88 physicians surveyed, 54 responded for a response rate of 61%. Respondents represented 37 of the 40 (93%) VHA radiation oncology departments (Table 1). Among respondents, most were board certified (96%), held academic appointments (91%), and were full-time employees (85%). Forty-four percent of respondents were in practice for > 20 years, 19% for 11 to 20 years, 20% for 6 to 10 years, and 17% for < 6 years. A majority reported familiarity with the ASTRO guidelines (64%), while just 11% reported no familiarity with the guidelines.

When asked about use of SBRT for palliation of hemoptysis, stridor, and/or chest pain, the majority (87%) preferred conventional EBRT. Of the 13% who reported use of SBRT, most (11%) performed it onsite, with 2% of respondents referring offsite to non-VHA centers for the service. When asked about use of EBB for palliation, only 2% reported use of that procedure at their facilities, while 26% reported referral to non-VHA facilities for EBB. The remaining 72% of respondents favor use of conventional EBRT.

Respondents were presented with a case of a male patient aged 70 years who smoked and had widely metastatic NSCLC, a life expectancy of about 3 months, and 10/10 chest wall pain from direct tumor invasion. All respondents recommended palliative radiotherapy. The preferred fractionation was 20 Gray (Gy) in 5 fractions, which was recommended by 69% of respondents. The remainder recommended 30 Gy in 10 fractions (22%) or a single fraction of 10 Gy (9%). No respondent recommended the longer fractionation options of 60 Gy in 30 fractions, 45 Gy in 15 fractions, or 40 Gy in 20 fractions. The majority (98%) did not recommend concurrent chemotherapy.

When the above case was modified for an endobronchial lesion requiring palliation with associated lung collapse, rather than chest wall invasion, 20 respondents (38%) reported they would refer for EBB, and 20 respondents reported they would refer for YAG laser. As > 1 answer could be selected for this question, there were 12 respondents who selected both EBB and YAG laser; 8 selected only EBB, and 8 selected only YAG laser. Many respondents added comments about treating with EBRT, which had not been presented as an answer choice. Nearly half of respondents (49%) were amenable to referral for the use of EBB or YAG laser for lung reexpansion prior to radiotherapy. Three respondents mentioned referral for an endobronchial stent prior to palliative radiotherapy to address this question.

Discussion

This survey was conducted to evaluate concordance of management of metastatic lung cancer in the VHA with ASTRO guidelines. The relationship between respondents’ familiarity with the guidelines and responses also was evaluated to determine the impact such guidelines have on decision-making. The ASTRO guidelines for palliative thoracic radiation make recommendations regarding 3 issues: (1) radiation doses and fractionations for palliation; (2) the role of EBB; and (3) the use of concurrent chemotherapy.^5,6

Radiation Dose and Fractionation for Palliation

A variety of dose/fractionation schemes are considered appropriate in the ASTRO guideline statement, including more prolonged courses such as 30 Gy/10 fractions as well as more hypofractionated regimens (ie, 20 Gy/5 fractions, 17 Gy/2 fractions, and a single fraction of 10 Gy). Higher dose regimens, such as 30 Gy/10 fractions, have been associated with prolonged survival, as well as increased toxicities such as radiation esophagitis.⁸ Therefore, the guidelines support use of 30 Gy/10 fractions for patients with good performance status while encouraging use of more hypofractionated regimens for patients with poor performance status. In considering more hypofractionated regimens, one must consider the possibility of adverse effects that can be associated with higher dose per fraction. For instance, 17 Gy/2 fractions has been associated with myelopathy; therefore it should be used with caution and careful treatment planning.⁹

For the survey case example (a male aged 70 years with a 3-month life expectancy who required palliation for chest wall pain), all respondents selected hypofractionated regimens; with no respondent selected the more prolonged fractionations of 60 Gy/30 fractions, 45 Gy/15 fractions, or 40 Gy/20 fractions. These more prolonged fractionations are not endorsed by the guidelines in general, and particularly not for a patient with poor life expectancy. All responses for this case selected by survey respondents are considered appropriate per the consensus guideline statement.

Role of Concurrent Chemotherapy

The ASTRO guidelines do not support use of concurrent chemotherapy for palliation of stage IV NSCLC.^5,6 The 2018 updated guidelines established a role for concurrent chemotherapy for patients with stage III NSCLC with good performance status and life expectancy of > 3 months. This updated recommendation is based on data from 2 randomized trials demonstrating improvement in overall survival with the addition of chemotherapy for patients with stage III NSCLC undergoing palliative radiotherapy.^10-12

These newer studies are in contrast to an older randomized study by Ball and colleagues that demonstrated greater toxicity from concurrent chemotherapy, with no improvement in outcomes such as palliation of symptoms, overall survival, or progression free survival.¹³ In contrast to the newer studies that included only patients with stage III NSCLC, about half of the patients in the Ball and colleagues study had known metastatic disease.^10-13 Of note, staging for metastatic disease was not carried out routinely, so it is possible that a greater proportion of patients had metastatic disease that would have been seen on imaging. In concordance with the guidelines, 98% of the survey respondents did not recommend concurrent chemotherapy for palliation of intrathoracic symptom; only 1 respondent recommended use of chemotherapy for palliation.

Role of Endobronchial Brachytherapy

EBB involves implantation of radioactive sources for treatment of endobronchial lesions causing obstructive symptoms.¹⁴ Given the lack of randomized data that demonstrate a benefit of EBB over EBRT, the ASTRO guidelines do not endorse routine use of EBB for initial palliative management.^15,16 The ASTRO guidelines reference a Cochrane Review of 13 trials that concluded that EBRT alone is superior to EBB alone for initial palliation of symptoms from endobronchial NSCLC.¹⁷

Of respondents surveyed, only 1 facility offered onsite EBB. The majority of respondents (72%) preferred the use of conventional EBRT techniques, while 26% refer to non-VHA centers for EBB. Lack of incorporation of EBB into routine VHA practice likely is a reflection of the unclear role of this technology based on the available literature and ASTRO guidelines. In the setting of a right lower lung collapse, more respondents (49%) would consider use of EBB or YAG laser technology for lung reexpansion prior to EBRT.

The ASTRO guidelines recommend that initial EBB in conjunction with EBRT be considered based on randomized data demonstrating significant improvement in lung reexpansion and in patient reported dyspnea with addition of EBB to EBRT over EBRT alone.¹⁸ However, the guidelines do not mandate the use of EBB in this situation. It is possible that targeted education regarding the role of EBB would improve knowledge of the potential benefit in the setting of lung collapse and increase the percentage of VHA ROs who would recommend this procedure.

Limitations

The study is limited by lack of generalizability of these findings to all ROs in the country. It is also possible that physician responses do not represent practice patterns with complete accuracy. The use of EBB varied among practitioners. Further study of this technology is necessary to clarify its role in the management of endobronchial obstructive symptoms and to determine whether efforts should be made to increase access to EBB within the VHA.

Conclusions

Most of the ROs who responded to our survey were cognizant and compliant with current ASTRO guidelines on management of lung cancer. Furthermore, familiarity with ASTRO guidelines and management choices were not associated with the respondents’ years in practice, academic appointment, full-time vs part-time status, or familiarity with ASTRO guidelines. This study is a nationwide survey of ROs in the VHA system that reflects the radiation-related care received by veterans with metastatic lung cancer. Responses were obtained from 93% of the 40 radiation oncology centers, so it is likely that the survey accurately represents the decision-making process at the majority of centers. It is possible that those who did not respond to the survey do not treat thoracic cases.