Radiation Therapy for HPV-Positive Oropharyngeal Squamous Cell Carcinoma: An ASTRO Clinical Practice Guideline.

PURPOSE: Human Papilloma Virus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is a distinct disease from other head and neck tumors. This guideline provides evidence-based recommendations on the critical decisions in its curative treatment, including both definitive and postoperative radiation therapy (RT) management. METHODS: ASTRO convened a task force to address 5 key questions on the use of RT for management of HPV-associated OPSCC. These questions included indications for definitive and postoperative RT and chemoradiation; dose-fractionation regimens and treatment volumes; preferred RT techniques and normal tissue considerations; and posttreatment management decisions. The task force did not address indications for primary surgery versus RT. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. RESULTS: Concurrent cisplatin is recommended for patients receiving definitive RT with T3-4 disease and/or 1 node >3 cm, or multiple nodes. For similar patients who are ineligible for cisplatin, concurrent cetuximab, carboplatin/5-fluorouracil, or taxane-based systemic therapy are conditionally recommended. In the postoperative setting, RT with concurrent cisplatin (either schedule) is recommended for positive surgical margins or extranodal extension. Postoperative RT alone is recommended for pT3-4 disease, >2 nodes, or a single node >3 cm. Observation is conditionally recommended for pT1-2 disease and a single node ≤3 cm without other risk factors. For patients treated with definitive RT with concurrent systemic therapy, 7000 cGy in 33 to 35 fractions is recommended, and for patients receiving postoperative RT without positive surgical margins and extranodal extension, 5600 to 6000 cGy is recommended. For all patients receiving RT, intensity modulated RT over 3-dimensional techniques with reduction in dose to critical organs at risk (including salivary and swallowing structures) is recommended. Reassessment with positron emission tomography-computed tomography is recommended approximately 3 months after definitive RT/chemoradiation, and neck dissection is recommended for convincing evidence of residual disease; for equivocal positron emission tomography-computed tomography findings, either neck dissection or repeat imaging is recommended. CONCLUSIONS: The role and practice of RT continues to evolve for HPV-associated OPSCC, and these guidelines inform best clinical practice based on the available evidence.

Evaluation of a novel patient-specific quality assurance phantom for robotic single-isocentre, multiple-target stereotactic radiosurgery, and stereotactic radiotherapy.

OBJECTIVES: To evaluate patient-specific quality assurance (PSQA) of 3 targets in a single delivery using a novel film-based phantom. METHODS: The phantom was designed to rotate freely as a sphere and could measure 3 targets with film in a single delivery. After identifying the coordinates of 3 targets in the skull, the rotation angles about the equator and meridian were computed for optimal phantom setup, ensuring the film plane intersected the 3 targets. The plans were delivered on the CyberKnife system using fiducial tracking. The irradiated films were scanned and processed. All films were analysed using 3 gamma criteria. RESULTS: Fifteen CyberKnife test plans with 3 different modalities were delivered on the phantom. Both automatic and marker-based registration methods were applied when registering the irradiated film and dose plane. Gamma analysis was performed using a 3%/1 mm, 2%/1 mm, and 1%/1 mm criteria with a 10% threshold. For the automatic registration method, the passing rates were 98.2% ± 1.9%, 94.2% ± 3.7%, and 80.9% ± 6.3%, respectively. For the marker-based registration approach, the passing rates were 96.4% ± 2.7%, 91.7% ± 4.3%, and 78.4% ± 6.2%, respectively. CONCLUSIONS: A novel spherical phantom was evaluated for the CyberKnife system and achieved acceptable PSQA passing rates using TG218 recommendations. The phantom can measure true-composite dose and offers high-resolution results for PSQA, making it a valuable device for robotic radiosurgery. ADVANCES IN KNOWLEDGE: This is the first study on PSQA of 3 targets concurrently on the CyberKnife system.

Recent Trends in Medicare Payments for Outpatient Cancer Care at the End of Life.

PURPOSE: Outpatient care for patients with cancer compromises 60% to 70% of health care costs during the last 6 months of life. Recent approvals for expensive biologics and growing support for lower-cost hypofractionated radiation therapy in the palliative management of advanced cancer have introduced offsetting spending effects on end-of-life care that may shift overall expenditures for this patient cohort. METHODS AND MATERIALS: In this descriptive retrospective cohort study, end-of-life care is defined as the aggregate of medical services and supplies, including drugs, furnished to patients with cancer in the outpatient setting during the last 6 months of life. A total of 84,744 Medicare beneficiaries with a cancer diagnosis were identified as having died between January 1, 2016, and December 31, 2019. Beneficiaries with Medicare Advantage were not included in this study. Medicare Standard Analytical Files were abstracted for all paid claims for these beneficiaries during the last 6 months of life, and provider payments were summed according to service or supply category and year of death. Comparisons of service and supply utilization and costs between patient groups were performed using the Pearson χ2 test. RESULTS: The average total Medicare Part B payments per treated beneficiary during the last 6 month of life increased by 12.0% between 2016 and 2019 (from $14,487 to $16,227), with the greatest absolute cost increase observed for the medical oncology category (from $7030 to $9436 [+34.2%]). Within the medical oncology category, drug utilization shifted away from less costly chemotherapy and hormone therapy agents and toward more expensive immunotherapy agents. The increase in immunotherapy utilization and drug costs alone accounted for 84% of the increase in total Part B payments for all categories during the period. CONCLUSIONS: Although costs related to end-of-life care for nearly all cost categories have remained relatively stable, oncology drug costs overall and immunotherapy costs specifically have accelerated and account almost entirely for the observed overall increase in outpatient cost burden for Medicare.

Lessons to Learn From a Successful Virtual Mock Oral Examination Pilot Experience.

oronavirus (COVID-19) has caused marked impact on graduate medical education for all medical specialties. Radiation Oncology and the American Board of Radiology have also had to rapidly adapt to converting education and examinations to virtual platforms. We describe our small pilot experience in transitioning our in-person mock oral examinations to a virtual platform. Survey-based assessment revealed excellent feedback regarding ease of use and educational usefulness. Our mock oral examinations pilot experience adds to evidence that virtual mock oral examinations are an important considerationfor Radiation Oncology education and a feasible alternative to an in-person oral examination.

Impact of Patient Stage and Disease Characteristics on the proposed Radiation Oncology Alternative Payment Model (RO-APM).

PURPOSE: The proposed Radiation Oncology Alternative Payment Model (RO-APM) released on July 10, 2019, represents a dramatic shift from fee-for-service (FFS) reimbursement in radiation therapy (RT). This study compares historical revenue at Mayo Clinic to the RO-APM and quantifies the effect that disease characteristics may have on reimbursement. METHODS AND MATERIALS: FFS Medicare reimbursements were determined for patients undergoing RT at Mayo Clinic from 2015 to 2016. Disease categories and payment episodes were defined as per the RO-APM. Average RT episode reimbursements were reported for each disease site, except for lymphoma and metastases, and stratified by stage and disease subcategory. Comparisons with RO-APM reimbursements were made via descriptive statistics. RESULTS: A total of 2098 patients were identified, of whom 1866 (89%) were categorized per the RO-APM; 840 (45%) of those were aged >65 years. Breast (33%), head and neck (HN) (14%), and prostate (11%) cancer were most common. RO-APM base rate reimbursements and sensitivity analysis range were lower than historical reimbursement for bladder (-40%), cervical (-34%), lung (-28%), uterine (-26%), colorectal (-24%), upper gastrointestinal (-24%), HN (-23%), pancreatic (-20%), prostate (-16%), central nervous system (-13%), and anal (-10%) and higher for liver (+24%) and breast (+36%). Historical reimbursement varied with stage (stage III vs stage I) for breast (+57%, P < .01), uterine (+53%, P = .01), lung (+50%, P < .01), HN (+24%, P = .01), and prostate (+13%, P = .01). Overall, for patients older than 65 years of age, the RO-APM resulted in a -9% reduction in total RT reimbursement compared with historical FFS (-2%, -15%, and -27% for high, mid, and low adjusted RO-APM rates). CONCLUSIONS: Our findings indicate that the RO-APM will result in significant reductions in reimbursement at our center, particularly for cancers more common in underserved populations. Practices that care for socioeconomically disadvantaged populations may face significant reductions in revenue, which could further reduce access for this vulnerable population.

Radiation therapy for oropharyngeal squamous cell carcinoma: Executive summary of an ASTRO Evidence-Based Clinical Practice Guideline.

PURPOSE: To present evidence-based guidelines for the treatment of oropharyngeal squamous cell carcinoma (OPSCC) with definitive or adjuvant radiation therapy (RT). METHODS AND MATERIALS: The American Society for Radiation Oncology convened the OPSCC Guideline Panel to perform a systematic literature review investigating the following key questions: (1) When is it appropriate to add systemic therapy to definitive RT in the treatment of OPSCC? (2) When is it appropriate to deliver postoperative RT with and without systemic therapy following primary surgery for OPSCC? (3) When is it appropriate to use induction chemotherapy in the treatment of OPSCC? (4) What are the appropriate dose, fractionation, and volume regimens with and without systemic therapy in the treatment of OPSCC? RESULTS: Patients with stage IV and stage T3 N0-1 OPSCC treated with definitive RT should receive concurrent high-dose intermittent cisplatin. Patients receiving adjuvant RT following surgical resection for positive surgical margins or extracapsular extension should be treated with concurrent high-dose intermittent cisplatin, and individuals with these risk factors who are intolerant of cisplatin should not routinely receive adjuvant concurrent systemic therapy. Induction chemotherapy should not be routinely delivered to patients with OPSCC. For patients with stage IV and stage T3 N0-1 OPSCC ineligible for concurrent chemoradiation therapy, altered fractionation RT should be used. CONCLUSION: The successful management of OPSCC requires the collaboration of radiation, medical, and surgical oncologists. When high-level data are absent for clinical decision-making, treatment recommendations should incorporate patient values and preferences to arrive at the optimal therapeutic approach.

Long-term survival of a patient with leptomeningeal involvement by nasopharyngeal carcinoma after treatment with high-dose intravenous methotrexate.

BACKGROUND: Nasopharyngeal carcinoma with leptomeningeal involvement is rare and typically has poor prognosis. METHODS AND RESULTS: We present a case report of a patient with nasopharyngeal carcinoma who was treated with high-dose intravenous methotrexate and remains asymptomatic and without clinical evidence of disease 6 years later. CONCLUSIONS: Systemic high-dose methotrexate should be evaluated in the treatment of advanced nasopharyngeal carcinoma with central nervous involvement.

Radiotherapeutic management of laryngeal carcinoma.

Authors discuss laryngeal lesions, metastases, and relevant anatomy. Outcome of surgical and radiotherapy in terms of voice preservation is discussed. Radiation techniques and outcomes for laryngeal cancer are presented along with discussion of interdisciplinary treatment. Authors review studies and quality of life outcomes of surviving laryngeal cancer patients.

A highly reproducible bolus immobilization technique for the treatment of scalp malignancies.

Radiation treatment of scalp malignancies can be a challenge due to the multiple curved surfaces to which homogenous dose must be delivered. The most readily available techniques utilize linear accelerator-based technique of opposed lateral electron field abutting opposed lateral photon field with central blocking. Bolus material is used to achieve adequate skin dose. Although plans to add bolus material often occur in the virtual setting during treatment planning, the practical aspects of reproducibly maintain the bolus material along curved surfaces during the day-to-day patient setup can be a challenge. We present a case of a patient with squamous cell carcinoma of the scalp with neck node involvement treated with surgery followed by adjuvant radiotherapy. We demonstrate a unique immobilization technique that maintains the bolus material on the aquaplast mesh adherent to the patient's scalp as well as the neck. TomoTherapy with daily megavoltage computed tomography (CT) scan was utilized to verify the daily bolus position. We were able to maintain a 95% reproducibility rate. This technique reliably maintains the bolus material on the desired locations with minimum adjustments and manipulation by the therapist and is a technique that can be universally adaptable for conventional radiotherapy or intensity modulated radiation therapy (IMRT) techniques.

Phase II study of imatinib mesylate in patients with prostate cancer with evidence of biochemical relapse after definitive radical retropubic prostatectomy or radiotherapy.

OBJECTIVES: Patients with biochemical recurrence of prostate cancer after definitive or salvage local therapy in the absence of metastatic disease represent a group well suited to a novel therapeutic intervention. Imatinib mesylate (Gleevec) is a protein-tyrosine kinase inhibitor that has previously been tested in men with androgen-independent and metastatic prostate cancer. This Phase II study was undertaken to determine the safety and efficacy of imatinib mesylate in men with biochemical relapse of nonmetastatic, androgen-sensitive prostate cancer after local therapy. METHODS: Twenty-seven patients were treated with imatinib mesylate 400 mg twice daily for up to 12 months. Three patients (11%) completed less than 4 weeks of therapy and were included in the intent-to-treat analysis of the response to therapy. RESULTS: Of the 27 patients treated, 5 (18.5%) had a stable prostate-specific antigen (PSA) during the course of treatment; 2 patients (7.4%) experienced a partial response. The remaining 20 patients (74.1%) demonstrated PSA progression. The median progression-free survival was 3 months. The proportion of patients achieving a partial PSA response during therapy did not significantly differ from the null rate of 5% (P = 0.394). Seven patients (25.9%) discontinued therapy secondary to grade 1 to 3 toxicities. No irreversible National Institutes of Health Common Toxicity Criteria grade 3 or 4 toxicities occurred. Grade 3 and 4 toxicity included leukopenia (3.7%), serum glutamic-oxaloacetic transaminase (3.7%) and serum glutamic-pyruvic transaminase (3.7%) elevation, and rash (18.5%). CONCLUSIONS: The results of our study have demonstrated that imatinib mesylate delivered at a dose of 400 mg twice daily is associated with a moderate degree of toxicity and a limited PSA response in this patient population.

Neck management in patients undergoing postradiotherapy salvage laryngeal surgery for recurrent/persistent laryngeal cancer.

OBJECTIVE: To determine a plan for the management of cervical lymph nodes in patients undergoing salvage laryngeal surgery (SLS) for recurrent/persistent laryngeal cancer after primary radiotherapy (RT). STUDY DESIGN: : Retrospective chart review. METHODS: Charts of 51 consecutive patients who had salvage total or supracricoid laryngectomy with or without neck dissection for recurrent/persistent laryngeal squamous cell carcinoma after primary RT from 1988 to 2005 in our institution were reviewed. No patients received concomitant or neo-adjuvant chemotherapy. Thirty-four patients underwent SLS along with unilateral or bilateral neck dissection, whereas 17 patients underwent the SLS without neck dissection. Reports of preRT and preSLS staging of the primary tumor and the neck, recorded using the TNM system, were reviewed. Reports of the final histopathologic examination for the excised laryngeal cancer and cervical lymph nodes were reviewed. RESULTS: Thirty-four patients underwent SLS with unilateral or bilateral neck dissection. The preRT staging of the primary tumor for those 34 patients showed that 32 (94%) were staged T-1 (14) and T-2 (18), whereas the preSLS staging of the primary tumor for those 34 patients showed that 29 (85%) were staged T-3 and T-4. The postSLS final histopathologic examination of the excised lymph nodes in those 34 patients demonstrated that 30 (88%) did not have any evidence of nodal metastasis. On comparing patients with and without nodal metastasis (on their postSLS final histopathology), we found that the preSLS neck staging, based on computed tomographic (CT) scanning of the neck, was significantly associated with the negative/positive postSLS status of nodal metastasis (P = .006). Of 29 patients staged preSLS as N-0, 28 (97%) patients did not have nodal metastasis on their postSLS final pathology (negative predictive value = 97%, confidence interval, 82.2-99.9). PreRT neck staging, preRT and preSLS staging of the primary tumor, along with laryngeal subsite involvement (supraglottis, glottis, subglottis) did not significantly correlate with the status of neck metastasis on final postSLS histopathology (P = .68, 0.78, 0.49, and 0.42, respectively). None of the 34 patients had any neck tumor recurrence in the postSLS follow-up period (median, 3 yr). In addition, all 17 patients who underwent SLS without neck dissection were staged N-0 both before RT as well as preSLS, and none developed neck disease in the postSLS follow-up period (median, 2.5 yr). CONCLUSION: Management of the neck in patients undergoing salvage total or supracricoid laryngectomy for laryngeal cancer recurrence/persistence after primary RT should be based on the preSLS CT staging of the neck. Patients staged N-0 preSLS are not likely to harbor occult nodal metastasis and therefore may not require elective neck dissection.

Current concepts and controversies in the treatment of parenchymal brain metastases: improved outcomes with aggressive management.

The multimodality management of brain metastases has undergone significant refinement in the last decade. Although brain metastases remain a significant source of morbidity and mortality for many cancer patients, aggresive management has led to pronounced gains in neurological functioning, disease free survival and overall survival compared to standard treatment regimens consisting of only whole brain radiation therapy. Representative studies reviewing the role of aggressive management approaches including surgical resection with or without whole brain radiation therapy or non-surgical approaches employing stereotactic radiosurgery alone or in combination with whole brain radiation therapy are highlighted. Additionally, the emerging role of systemic agents showing distinct clinical activity in patients with brain metastases are also discussed. As we continue to gain advances in systemic therapies for metastatic disease, local control of brain metastases in these patients is likely to become more critical in improving survival and quality of life, thereby calling for a more aggressive multi-modal approach to this population of patients.

Treatment of complications after breast-conservation therapy.

Over the past 2 decades, breast-conservation therapy with lumpectomy and whole-breast radiotherapy has become a standard option for the majority of women with newly diagnosed breast cancer. Long-term local control is achieved in approximately 85% of patients, and the therapy is generally well tolerated. There can, however, be long-term effects on the breast and other nearby tissues that may range from asymptomatic findings on examination to severe, debilitating problems. Infection, fat necrosis, and severe musculoskeletal problems such as osteoradionecrosis or soft-tissue necrosis are uncommon, affecting less than 5% of patients. However, changes in range of motion, mild-to-moderate musculoskeletal pain, and arm and breast edema are much more common. As more women choose breast-conservation therapy for management of their breast cancer, physicians will encounter these problems, as well as in-breast tumor recurrence, with greater frequency. This review will focus on the incidence, contributing factors, and management of the late problems of infection, fat necrosis, musculoskeletal complications, and local recurrence following breast-conservation therapy.