Single-fraction radiation retreatment for bone metastases: role of a rapid access clinic.

OBJECTIVES: This study investigates retreatment rates in single-fraction radiation therapy (SFRT) for painful bone metastasis in patients with limited life expectancy. We compared retreatment-free survival (RFS) in patients from a rapid access bone metastases clinic (RABC) and non-RABC patients, identifying factors associated with retreatment. METHODS: In this observational study, we analysed RABC patients who received SFRT between April 2018 and November 2019, using non-RABC SFRT patients as a comparison group. Patients with prior or perioperative radiation therapy (RT) were excluded. The primary endpoint was same-site and any-site retreatment with RT or surgery. Patient characteristics were compared using χ2 and Student's t-tests, with RFS estimates based on a multistate model considering death as a competing risk using Aalen-Johansen estimates. RESULTS: We identified 151 patients (79 RABC, 72 non-RABC) with 225 treatments (102 RABC, 123 non-RABC) meeting eligibility criteria. Of the 22 (10.8%) same-site retreatments, 5 (22.7%) received surgery, 14 (63.6%) received RT and 3 (13.6%) received both RT and surgery. We found no significant differences in any-site RFS (p=0.97) or same-site RFS (p=0.11). CONCLUSIONS: RFS is high and similar comparable in the RABC and non-RABC cohorts. Retreatment rates are low, even in patients with low Eastern Cooperative Oncology Group scores.

A simple solution to create a custom scalp-sparing helmet to prevent alopecia in patients undergoing total skin electron beam therapy for cutaneous T cell lymphoma.

Total skin electron beam therapy (TSEBT) is effective for patients with refractory or diffuse skin involvement of cutaneous T cell lymphomas (CTCL). A common concern for patients undergoing TSEBT is the development of alopecia. Patients are already burdened with the physical symptoms associated with their disease; therefore, mitigating additional physical side effects of treatment, including cosmetic concerns, is important. As such, the purpose of this study is to evaluate a novel technique to prevent alopecia after TSEBT. Prior scalp sparing techniques have relied largely on materials found in the radiation department (e.g., lead, Superflab bolus), but in this report, we utilized a custom blue wax polyethylene material to create a custom scalp-sparing, dose attenuating, helmet. The priorities that lead to investigating this solution included patient comfort, full scalp protection, and practicality. We wanted to find a light weight, snug fitting, helmet to protect the entire hair line, that could be easily fabricated for any patient. In the end, we found success in our efforts to minimize radiation to the scalp for indistinguishable hair volume changes.

A Machine Learning Model Approach to Risk-Stratify Patients With Gastrointestinal Cancer for Hospitalization and Mortality Outcomes.

PURPOSE: Patients with gastrointestinal (GI) cancer frequently experience unplanned hospitalizations, but predictive tools to identify high-risk patients are lacking. We developed a machine learning model to identify high-risk patients. METHODS AND MATERIALS: In the study, 1341 consecutive patients undergoing GI (abdominal or pelvic) radiation treatment (RT) from March 2016 to July 2018 (derivation) and July 2018 to January 2019 (validation) were assessed for unplanned hospitalizations within 30 days of finishing RT. In the derivation cohort of 663 abdominal and 427 pelvic RT patients, a machine learning approach derived random forest, gradient boosted decision tree, and logistic regression models to predict 30-day unplanned hospitalizations. Model performance was assessed using area under the receiver operating characteristic curve (AUC) and prospectively validated in 161 abdominal and 90 pelvic RT patients using Mann-Whitney rank-sum test. Highest quintile of risk for hospitalization was defined as "high-risk" and the remainder "low-risk." Hospitalizations for high- versus low-risk patients were compared using Pearson's χ2 test and survival using Kaplan-Meier log-rank test. RESULTS: Overall, 13% and 11% of patients receiving abdominal and pelvic RT experienced 30-day unplanned hospitalization. In the derivation phase, gradient boosted decision tree cross-validation yielded AUC = 0.823 (abdominal patients) and random forest yielded AUC = 0.776 (pelvic patients). In the validation phase, these models yielded AUC = 0.749 and 0.764, respectively (P < .001 and P = .002). Validation models discriminated high- versus low-risk patients: in abdominal RT patients, frequency of hospitalization was 39% versus 9% in high- versus low-risk groups (P < .001) and 6-month survival was 67% versus 92% (P = .001). In pelvic RT patients, frequency of hospitalization was 33% versus 8% (P = .002) and survival was 86% versus 92% (P = .15) in high- versus low-risk patients. CONCLUSIONS: In patients with GI cancer undergoing RT as part of multimodality treatment, machine learning models for 30-day unplanned hospitalization discriminated high- versus low-risk patients. Future applications will test utility of models to prompt interventions to decrease hospitalizations and adverse outcomes.

Outcomes after salvage for HPV-positive recurrent oropharyngeal cancer treated with primary radiation.

PURPOSE: HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) carries a favorable prognosis for patients, yet nearly 30% of patients will experience disease relapse. We sought to detail patterns of failure, associated salvage therapy, and outcomes for patients with recurrent HPV-positive OPSCC. METHODS AND MATERIALS: This is a single institution retrospective study of patients with recurrent HPV-positive OPSCC irradiated from 2002 to 2014. The primary study outcome was overall survival (OS, calculated using the Kaplan-Meier method). Secondary aims included patterns of first failure with descriptive details of salvage therapy. Solitary recurrences were defined as initial presentation of recurrence in a single site (primary, neck or oligometastatic), and multi-site was defined as local and regional and/or multiple sites of distant recurrence. Survival outcomes were compared using the log-rank test. RESULTS: The cohort consisted of 132 patients. The median follow-up was 59 months for surviving patients. Estimated 2-year and 5-year OS rates were 47% and 32%, respectively. Comparative 2-year and 5-year OS rates were 65% and 46% versus 19% and 9% for the solitary group and multi-site group, respectively (p < .001). CONCLUSIONS: Patients with recurrent HPV-positive OPSCC experience 5-year survival of approximately 32%. However, patients with a "solitary" recurrence including disease at the primary site, neck or oligometastatic site have more favorable long-term outcomes.

Partial omission of bleomycin for early-stage Hodgkin lymphoma patients treated with combined modality therapy: Does incomplete ABVD lead to inferior outcomes?

Classical Hodgkin lymphoma (HL) patients achieve excellent outcomes; therefore, treatment de-escalation strategies to spare toxicity have been prioritized. In a large randomized trial of early stage HL patients, omission of chemotherapeutic agents including bleomycin from the standard ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) regimen was not found to be non-inferior; however the effect of partial omission is unknown. We investigated the effect of bleomycin omission on outcome for 150 early stage HL patients. At eight years, freedom from relapse was 99% for both patients who received complete or incomplete bleomycin, which is reassuring for patients requiring bleomycin omission due to toxicity.

Decreased heart dose with deep inspiration breath hold for the treatment of gastric lymphoma with IMRT.

We hypothesized that deep inspiration breath-hold (DIBH) and computed-tomography image-guided radiotherapy (CT-IGRT) may be beneficial to decrease dose to organs at risk (OARs), when treating the stomach with radiotherapy for lymphoma. We compared dosimetric parameters of OARs from plans generated using free-breathing (FB) versus DIBH for 10 patients with non-Hodgkin lymphoma involving the stomach treated with involved site radiotherapy. All patients had 4DCT and DIBH scans. Planning was performed with intensity modulated radiotherapy (IMRT) to 30.6 Gy in 17 fractions. Differences in target volume and dosimetric parameters were assessed using a paired two-sided t-test. All heart and left ventricle parameters including mean dose, V30, V20, V10, and V5 were statistically significantly lower with DIBH. For IMRT-FB plans the average mean heart dose was 4.9 Gy compared to 2.6 Gy for the IMRT-DIBH group (p < 0.001). There was a statistically significant decrease in right kidney dose with DIBH. For lymphoma patients treated to the stomach with IMRT, DIBH provides superior OAR sparing compared to FB-based planning, most notably reducing dose to the heart and left ventricle. This strategy could be considered when treating other gastric malignancies.

Outcomes of Curative-Intent Treatment for Patients With Breast Cancer Presenting With Sternal or Mediastinal Involvement.

PURPOSE: Optimal treatment of patients diagnosed with de novo metastatic breast cancer limited to the mediastinum or sternum has never been delineated. Herein, we sought to determine the efficacy of multimodality treatment, including metastasis-directed radiation therapy, in curing patients with this presentation. METHODS AND MATERIALS: This is a single-institution retrospective cohort study of patients with de novo metastatic breast cancer treated from 2005 to 2014, with a 50-month median follow-up for the primary cohort. The primary patient cohort had metastasis limited to the mediastinum/sternum treated with curative intent (n = 35). We also included a cohort of patients with stage IIIC disease treated with curative intent (n = 244). Additional groups included a mediastinal/sternal palliative cohort (treatment did not include metastasis-directed radiation therapy; n = 14) and all other patients with de novo stage IV disease (palliative cohort; n = 1185). The primary study outcomes included locoregional recurrence-free survival (LRRFS), recurrence-free survival (RFS), and overall survival (OS), which were calculated using the Kaplan-Meier method. Cox multivariable models compared survival outcomes across treatment cohorts adjusted for molecular subtype, age, and race. RESULTS: For the mediastinal/sternal curative-intent cohort, 5-year LRRFS was 85%, RFS was 52%, and OS was 63%. After adjustment, there was no statistically significant difference in LRRFS (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.13-1.13; P = .08), RFS (HR, 0.87; 95% CI 0.50-1.49; P = .61), or OS (HR, 0.79; 95% CI 0.44-1.43; P = .44) between the stage IIIC cohort and the mediastinal/sternal curative-intent cohort (referent). In contrast, RFS was worse for the mediastinal/sternal palliative cohort (HR, 2.29; 95% CI 1.05-5.00; P = .04). OS was worst for the de novo stage IV palliative cohort (HR, 2.61; 95% CI 1.50-4.53; P < .001). CONCLUSIONS: For select patients presenting with breast cancer metastatic to the sternum and/or mediastinum, curative-intent treatment with chemotherapy, surgery, and radiation yields outcomes similar to those of stage IIIC disease and superior to de novo stage IV breast cancer treated with palliative intent.

Lingual Tonsillectomy Likely Does Not Improve Outcomes for Squamous Cell Carcinoma of the Head and Neck From an Unknown Primary Site.

OBJECTIVE: Patients with mucosal squamous cell carcinoma (SCC) of the head and neck almost always have a primary site in the base of tongue or tonsillar fossa. Lingual tonsillectomy has recently been advocated as part of the diagnostic evaluation as opposed to directed biopsies of the base of tongue and thought to possibly result in an increased likelihood or cure. The purpose of this project is to determine whether this is probable. MATERIALS AND METHODS: We reviewed the medical records of patients treated with primary radiotherapy (RT) between January 1983 and March 2013. The outcomes were compared following RT in consecutively treated patients with either T1-2 base of tongue or unknown primary (cancer of unknown primary) SCC with predominantly level 2 adenopathy. RESULTS: At 10 years, there were no clinically significant differences in the 2 groups, in local control, regional control, freedom from distant metastases, disease-specific, or cause-specific survival. Overall survival at 10 years was improved with T1-2 base of tongue cancers but not for those with T0 N3 disease. The reasons for this are unclear. CONCLUSIONS: Tongue base biopsy (or lingual tonsillectomy) likely increases the probability of identifying an unknown primary in the base of tongue, but it does not improve outcome following RT for patients with cancer of unknown primary SCC with predominantly level 2 adenopathy.

How Does MR Imaging Help Care for My Breast Cancer Patient? Perspective of a Radiation Oncologist.

Radiation therapy is used in many cases of both early and late breast cancer. The authors examine the role of MR imaging as it pertains to radiotherapy planning and treatment approaches for patients with breast cancer. MR imaging can assist the radiation oncologist in determining the best radiation approach and in creating treatment planning volumes. MR imaging may be useful in the setting of accelerated partial breast irradiation. Radiation oncologists should attend to MR breast images, when obtained, to ensure that these imaging findings are taken into consideration when developing a radiation therapy plan.

Radiotherapy alone or combined with chemotherapy for base of tongue squamous cell carcinoma.

OBJECTIVES/HYPOTHESIS: To evaluate the long-term disease control, survival, and complications after definitive radiotherapy (RT) alone or combined with adjuvant chemotherapy with or without planned neck dissection for base of tongue squamous cell carcinoma (SCC). STUDY DESIGN: We retrospectively reviewed the medical records of 467 patients treated at the University of Florida with definitive RT alone or combined with adjuvant chemotherapy between 1964 and 2011 for base of tongue SCC. METHODS: Median follow-up was 5.6 years. Median total dose to the primary site was 74.4 Gy. Eighty-seven patients (19%) were treated with once-daily fractionation, and 380 (81%) received altered fractionation schedules. Intensity-modulated RT was used in 128 patients (27%). Chemotherapy was administered to 173 (37%) patients. Planned neck dissection after RT was performed in 226 patients (48%). Data regarding p16 pathway activation were available for 25 patients. RESULTS: At 5 years, the local, local-regional, and regional control rates were 85.5%, 80.0%, and 90.0%, respectively. The 5-year overall, cause-specific, and distant metastasis-free survival rates were 59.1%, 71.5%, and 84.1%, respectively. Sixty-four patients (14%) developed one or more severe late complications. Fifty patients (11%) required late gastrostomy tube placement. CONCLUSIONS: This study supports the continued use of RT alone or combined with adjuvant chemotherapy for patients with base of tongue SCC, as this treatment yields high rates of cause-specific survival and disease control, with a relatively low rate of late complications. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:1589-1594, 2017.

Base of tongue squamous cell carcinoma with infiltrative bone marrow carcinomatosis after definitive chemoradiation: A case report.

BACKGROUND: Oropharyngeal squamous cell carcinoma (SCC) is known for its propensity for aggressive local progression and regional lymphatic spread. Distant metastases are relatively uncommon and the likelihood of hematogenous dissemination is primarily related to the extent and location of cervical lymph node metastases. Common sites of distant metastasis include the liver and lung. METHODS: We report an unusual case of base of tongue SCC with infiltrative bone marrow carcinomatosis presenting months after definitive chemoradiation despite locoregional control. RESULTS: Our patient exhibited an unusual pattern of distant dissemination after definitive chemoradiation had resulted in locoregional control. CONCLUSION: Patients who present with bone marrow failure after definitive treatment with apparent disease control should be monitored for bone marrow infiltration by the tumor and, if such infiltration is present, should be evaluated for palliative chemotherapy. Unfortunately, the prognosis for such patients is poor. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2449-E2453, 2016.

Radiation therapy for mucosal melanoma of the head and neck.

OBJECTIVES: The aim of this study was to evaluate the long-term effectiveness and complications of radiotherapy (RT) in the treatment of patients with mucosal melanomas of the head and neck. MATERIALS AND METHODS: The medical records of 21 patients treated with definitive or postoperative (RT) between 1974 and 2011 at the University of Florida Department of Radiation Oncology in Gainesville, FL, and the University of Florida Proton Therapy Institute in Jacksonville, FL, were retrospectively reviewed under an Institutional Review Board-approved protocol. Primary sites included nasal cavity, oropharynx, and paranasal sinuses. Sixteen patients (76%) received surgery and postoperative RT and 5 patients (24%) received RT alone. Seventeen patients received photon RT alone, whereas 4 patients received combined photon-based and proton-based RT. Median follow-up for all patients was 1.05 years (range, 0.36 to 12.97 y); median follow-up for survivors was 2.2 years (range 0.9 to 13.0 y). RESULTS: The 5-year outcomes were: local control, 79%; regional control, 85%; local-regional control, 65%; distant metastasis-free survival, 20%; cause-specific survival, 22%; and overall survival, 22%. Three patients (14%) experienced severe complications including bilateral blindness and skin necrosis. CONCLUSIONS: Definitive or postoperative RT for mucosal melanoma of the head and neck yields fairly good local-regional control of disease. The prognosis for patients treated with definitive RT is less promising than for those who receive surgery and postoperative RT.

Local control in non-metastatic medulloblastoma.

BACKGROUND: A single-institution review of long-term outcomes and factors affecting local control (LC) following radiotherapy for non-metastatic medulloblastoma. MATERIAL AND METHODS: From 1963 to 2008, 50 children (median age, 7.3 years; range 1.2-18.5) with stage M0 medulloblastoma were treated with radiotherapy; half underwent a gross total resection (no visible residual tumor) or near-total resection (< 1.5 cm(3) of gross disease remaining after resection). Median craniospinal dose was 28.8 Gy (range 21.8-38.4 Gy). Median total dose to the posterior fossa was 54.3 Gy (range 42.4-64.8 Gy). Eighteen patients (36%) received chemotherapy as part of multimodality management, including 11 who received concurrent chemotherapy. RESULTS: Median follow-up was 15.7 years (range 0.3-44.4 years) for all patients and 26.6 years (range 7.3-44.4 years) for living patients. The 10-year overall survival, cancer-specific survival, and progression-free survival rates were 65%, 65%, and 69%. The 10-year LC rate was 84% and did not significantly change across eras. Four percent of patients experienced local progression five years after treatment. On univariate analysis, chemotherapy and overall duration of radiotherapy ≤ 45 days were associated with improved LC. Patients receiving chemotherapy had a 10-year 100% LC rate versus 76% in patients not receiving chemotherapy (p = 0.0454). When overall radiotherapy treatment lasted ≤ 45 days, patients experienced a superior 95% 10-year LC rate (vs. 73% in patients treated > 45 days; p = 0.0419). Three patients (6%) died from treatment complications, including radionecrosis/cerebellar degeneration, severe cerebral edema leading to herniation, and secondary malignancy. CONCLUSIONS: While we cannot draw definitive conclusions given the retrospective nature of our study, our long-term data suggest that reductions in craniospinal dose and boost target volume to reduce toxicity have not compromised disease control in the modern era. Our data also support analyses that implicate duration of radiotherapy, rather than interval between surgery and radiotherapy, as a factor in LC. Chemotherapy in multimodality management of medulloblastoma may have an underappreciated role in improving LC rates.

Late toxicity following craniospinal radiation for early-stage medulloblastoma.

BACKGROUND: The purpose of this study is to review late toxicity following craniospinal radiation for early-stage medulloblastoma. MATERIAL AND METHODS: Between 1963 and 2008, 53 children with stage M0 (n = 50) or M1 (n = 3) medulloblastoma were treated at our institution. The median age at diagnosis was 7.1 years (range 1.2-18.5). The median craniospinal irradiation (CSI) dose was 28.8 Gy (range 21.8-38.4). The median total dose, including boost, was 54 Gy (range 42.4-64.8 Gy). Since 1963, the CSI dose has been incrementally lowered and the high-risk boost volume reduced. Twenty-one patients (40%) received chemotherapy in their initial management, including 12 who received concurrent chemotherapy. Late sequelae were evaluated by analyzing medical records and conducting phone interviews with surviving patients and/or care-takers. Complications were graded using the NCI Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: The median follow-up for all patients was 15.4 years (range 0.4-44.4) and for living patients it was 24 years (range 5.6-44.4). The overall survival, cause-specific survival, and progression-free survival rates at 10 years were 67%, 67%, and 71%, respectively. Sixteen patients (41% of patients who survived five years or more) developed grade 3 + toxicity; 15 of these 16 patients received a CSI dose > 23.4 Gy. The most common grade 3 + toxicities for long-term survivors are hearing impairment requiring intervention (20.5%) and cognitive impairment (18%) prohibiting independent living. Four patients developed secondary (non-skin) malignancies, including three meningiomas, one rhabdomyosarcoma, and one glioblastoma multiforme. Three patients (5.6%) died from treatment complications, including radionecrosis, severe cerebral edema, and fatal secondary malignancy. CONCLUSION: Ongoing institutional and cooperative group efforts to minimize radiation exposure are justified given the high rate of serious toxicity observed in our long-term survivors. Follow-up through long-term multidisciplinary clinics is important and warranted for all patients exposed to radiotherapy in childhood.

Radiotherapy for sinonasal undifferentiated carcinoma.

PURPOSE: To evaluate the long-term effectiveness of radiotherapy (RT) in the treatment of sinonasal undifferentiated carcinoma (SNUC). MATERIALS AND METHODS: The medical records of 23 patients treated with definitive or postoperative RT between 1992 and 2010 at the University of Florida were retrospectively reviewed. Fifteen patients (65%) received primary surgery and postoperative RT. Radiation doses ranged from 59.0 to 74.8 Gy (median, 70.2 Gy). The median follow-up time for all patients was 3.0 years (range, 0.9-19.9), and for living patients was 7.7 years (range, 2.5-19.9). RESULTS: The actuarial 5-year survival outcomes were as follows: progression-free survival, 42%; cause-specific survival, 43%; and overall survival, 32%. Actuarial 5-year disease control rates were as follows: local control (infield or marginal), 74%; local-regional control (excluding leptomeningeal spread), 58%, regional control 78%, freedom from leptomeningeal recurrence, 72%, and distant metastasis-free survival, 73%. Five of the 8 (62.5%) patients treated with definitive RT died with disease, and 6 of the 15 patients (40%) treated with primary surgery and postoperative RT died with disease. Three patients (13%) experienced severe complications including unilateral eye removal, osteoradionecrosis of the maxilla requiring hyperbaric oxygen and surgery, and brain necrosis. One patient died due to an infected bone graft and brain abscess. CONCLUSIONS: A multimodal approach is best when treating SNUC patients. The prognosis for patients treated with definitive RT ± chemotherapy is less promising than for those who receive surgery and postoperative RT ± chemotherapy. Severe complications occur in about 17% of patients due to the high dose of RT alone or combined with surgery required for acceptable disease control.