Proton Beam Therapy in Liver Malignancies.

PURPOSE OF REVIEW: Proton beam therapy (PBT) allows for improved sparing of surrounding normal tissues compared with X-ray-based radiation therapy. This is especially important in the setting of liver malignancies, where an increase in integral dose leads to a higher risk of radiation-induced liver disease (RILD) as well as close proximity to vital gastrointestinal (GI) organs. RECENT FINDINGS: We have data from multiple centers demonstrating that PBT can safely deliver high, ablative doses of radiation therapy conferring excellent local control with good tolerance of treatment. PBT is an effective treatment with longstanding evidence of efficacy that is increasing in availability.

Factors Predictive of Receiving Adjuvant Radiotherapy in High-Intermediate-Risk Stage I Endometrial Cancer.

OBJECTIVES: Randomized trials have shown a local control benefit with adjuvant radiotherapy (RT) in high-intermediate-risk endometrial cancer patients, although not all such patients receive RT. We reviewed the National Cancer Data Base to investigate which patient/tumor-related factors are associated with delivery of adjuvant RT. METHODS: The National Cancer Data Base was queried for patients diagnosed with International Federation of Gynecology and Obstetrics 2009 stage I endometrioid adenocarcinoma from 1998 to 2012 who underwent surgery +/- adjuvant RT. Exclusion criteria were unknown stage/grade, nonsurgical primary therapy, less than 30 days' follow-up, RT of more than 6 months after surgery, or palliative treatment. High-intermediate risk was defined based on Post Operative Radiation Therapy in Endometrial Carcinoma 2 criteria: older than 60 years with stage IA grade 3 or stage IB grade 1-2. RESULTS: Seventeen thousand five hundred twenty-four met inclusion criteria, and the 13,651 patients with complete data were subjected to a multiple logistic regression analysis; 7814 (57.2%) received surgery alone, and 5837 (42.8%) received surgery + RT. Receipt of adjuvant RT was more likely among black women and women with higher income, Northeastern residence, diagnosis after 2010, greater than 50% myometrial invasion, and receipt of adjuvant chemotherapy (P < 0.05). Patients older than 80 years or those undergoing lymph node dissection were less likely to receive adjuvant RT (P < 0.05). Of those treated with RT, 44.0% received external beam therapy, 54.8% received vaginal cuff brachytherapy, and 0.6% received both. Among irradiated women, patients older than 80 years and those with Northeastern residence, treatment at academic facilities, diagnosis after 2004, and lymph node dissection were more likely to undergo brachytherapy over external beam radiation therapy (P < 0.05). Overall use of adjuvant RT was 28.8% between 1998 and 2004, 42.0% between 2005 and 2010, and 43.4% between 2011 and 2012; the difference between 1998-2004 and 2005-2010 was not statistically significant. CONCLUSIONS: Fewer than half of patients with high-intermediate-risk endometrial cancer by Post Operative Radiation Therapy in Endometrial Carcinoma 2 criteria received adjuvant RT despite evidence demonstrating improved local control. Both patient- and tumor-related factors are associated with delivery of adjuvant RT and the modality selected.

Clinical Outcomes of Intensity Modulated Proton Therapy Reirradiation for Gynecologic Malignancies.

Purpose: Pelvic reirradiation (re-RT) for patients with gynecologic cancers remains a challenge because of toxicity concerns. Given the dosimetric advantages of proton therapy, we aimed to assess oncologic and toxicity outcomes of patients with re-RT to the pelvis/abdomen with intensity modulated proton therapy (IMPT) for gynecologic cancers. Methods and Materials: We performed a retrospective analysis of all patients with gynecologic cancer treated at a single institution between 2015 and 2021 with IMPT re-RT. Patients were included for analysis if the IMPT plan had at least partial overlap with the treated volume of a previous radiation treatment. Results: A total of 29 patients were included for analysis, with 30 total courses of re-RT. The majority of patients had been treated previously with conventional fractionation to a median dose of 49.2 Gy (30-61.6 Gy). With a median follow-up of 23 months, 1-year local control was 83.5% and overall survival was 65.7%. Three patients (10%) developed acute and late grade 3 toxicity. One-year freedom from late grade 3+ toxicity was 96.3%. Conclusions: This is the first complete analysis of clinical outcomes for re-RT with IMPT for gynecologic malignancies. We demonstrate excellent local control and acceptable acute and late toxicity. IMPT should strongly be considered for treatments requiring re-RT for gynecologic malignancies.

Post-treatment PET/CT for p16-positive oropharynx cancer treated with definitive proton therapy.

Objectives: Given emerging data suggesting that uncertainty in the relative biologic effectiveness at the distal end of the Bragg peak results in increased mucosal injury in patients with oropharynx cancer receiving adjuvant proton therapy, we evaluated the results of post-treatment positron emission tomography-computed tomography (PET/CT) in patients with p16-positive oropharynx cancer (p16+OPC) treated with definitive intensity-modulated proton therapy (IMPT). Material and Methods: A retrospective cohort study of patients with p16+OPC treated with definitive IMPT between 2016 and 2022 was performed at a single institution. Patients with PET/CT scans within 6 months following completion of IMPT were included in the study. Positive post-treatment scans were defined by a maximum standard uptake values (SUVmax) >4.0 or a <65% reduction in SUVmax in either the primary tumor or lymph node. The Fisher's exact test was used to evaluate factors associated with positive post-treatment PET/ CT values. Results: Sixty-two patients were included for analysis. Median follow-up was 21 months (range: 3-71 months) with a median time to post-treatment PET/CT of 3 months (range: 2-6 months). Median post-treatment SUVmax of the primary disease and nodal disease was 0 (mean: 0.8, range: 0-7.7) and 0 (mean: 0.7, range: 0-9.5), respectively. Median post-treatment percent reduction in SUVmax for the primary site and lymph node was 100% (mean: 94%, range: 31.3-100%) and 100% (mean: 89%, range: 23-100%), respectively. Eleven patients had a positive post-treatment PET/CT with one biopsy-proven recurrence. Negative and positive predictive values (NPV and PPV) were 98% and 9.1%, respectively. There were no factors associated with positive post-treatment PET/CT. Conclusion: Similar to patients treated with photon-based radiation therapy, post-treatment PET/CT has a high NPV for patients with p16+OPC treated with definitive proton therapy and should be used to guide patient management. Additional patients and more events are needed to confirm the PPV of a post-treatment PET/CT in this favorable patient cohort.

Gross tumor volume margin and local control in p16-positive oropharynx cancer patients treated with intensity modulated proton therapy.

BACKGROUND: To determine if the extent of high-dose gross tumor volume (GTV) to clinical target volume (CTV) expansion is associated with local control in patients with p16-positive oropharynx cancer (p16+ OPC) treated with definitive intensity modulated proton therapy (IMPT). METHODS: We performed a retrospective analysis of patients with p16+ OPC treated with IMPT at a single institution between 2016 and 2021. Patients with a pre-treatment PET-CT and restaging PET-CT within 4 months following completion of IMPT were analyzed. RESULTS: Sixty patients were included for analysis with a median follow-up of 17 months. The median GTV to CTV expansion was 5 mm (IQR: 2 mm). Thirty-three percent of patients (20 of 60) did not have a GTV to CTV expansion. There was one local failure within the expansion group (3%). CONCLUSION: Excellent local control was achieved using IMPT for p16+ OPC independent of GTV expansion. IMPT with minimal target expansions represent a potential harm-minimization technique for p16-positive oropharynx cancer.

Assessing the Need for Adjusted Organ-at-Risk Planning Goals for Patients Undergoing Adjuvant Radiation Therapy for Locally Advanced Breast Cancer with Proton Radiation.

PURPOSE: Locally advanced breast cancer requires surgical management via lumpectomy or mastectomy with or without systemic therapy followed by chest wall or breast (CW) and comprehensive nodal irradiation (CNI). Radiation (RT) dose constraints for the heart and ipsilateral lung have been developed based on photon RT. Proton therapy (PBT) can deliver significantly lower doses of RT to these organs-at-risk (OARs) and may warrant adjustments to OAR planning goals. METHODS AND MATERIALS: The RT plans of consecutive patients undergoing adjuvant CW-CNI RT with PBT within a single center were reviewed. A inital treatment volume, comprised of CW/intact breast + CNI (CTV_init) structure, including the CW and CNI but excluding any boost plans was analyzed. Frequency distributions were generated based on doses received by the heart, lungs, and esophagus for validated dosimetric parameters. Frequency distributions were generated and then stratified by laterality and compared using the Kruskal-Wallis H test. The 75th, 85th, and 95th percentiles for each dosimetric parameter were calculated, overall and by laterality. The 75th percentile (Q3), was used as a suggested primary goal, and the 95th percentile was used as a suggested secondary goal. RESULTS: One hundred and seventy-two plans were analyzed. Forty-nine plans were right-sided, 107 were left-sided, and 16 were bilateral. The overall Q3 of the mean and V25 of the heart were 1.5 Gy and 1.7%, respectively. The mean and V25 to the heart differed significantly by laterality. Pulmonary values were similar to current recommendations. For all lateralites, the median volume of the esophagus receiving 70% prescription dose was ≤1 cm3. CONCLUSIONS: We present the first dosimetric study providing complete OAR dose-volume histograms data for patients undergoing adjuvant pencil-beam scanning-PBT for locally advanced breast cancer, with detailed information on central tendencies, ranges and distributions of data. We have provided suggested planning goals and metrics for the lungs, heart, and esophagus; the latter 2 differing significantly from current Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) constraints and classical photon goals.

Amifostine- and chemoradiotherapy-related esophagitis in small cell lung cancer: a single institutional series and literature update.

OBJECTIVES: Concurrent chemoradiotherapy is considered a standard option for patients with stage 3 small cell lung carcinoma. A 25% risk of acute esophagitis is experienced by patients as a result of the volume of esophagus encompassed within a conformal radiotherapy technique. We reviewed our institutional experience administering the radioprotectant amifostine prior to daily radiotherapy to determine its effects on the onset of esophagitis. MATERIALS AND METHODS: From 2005 to 2016, 49 patients diagnosed with stage 3 small cell lung carcinoma received concurrent chemoradiotherapy. Chemotherapy (CT) consisted of cisplatin and etoposide with radiotherapy (RT) encompassing CT-identified gross tumor volume. In 32 patients (group 1), amifostine was delivered (500 mg subcutaneously divided in two injections) prior to the second daily RT fraction. The remaining 17 patients (group 2) did not receive amifostine due to choice or drug intolerance. RESULTS: Metrics of esophagitis included weight loss and opiate requirement during treatment. About 31% of group 1 required opiates at a median RT dose of 3300 cGy, and 41% of group 2 required opiates at a median dose of 2250 cGy. The dose of radiotherapy delivered to 50% of the esophageal volume for group 1 was significantly greater than that in group 2 (3000 cGy vs 576 cGy). CONCLUSION: In this modern retrospective series of thoracic chemoradiotherapy in the treatment of stage 3 small cell lung cancer, amifostine that was delivered subcutaneously postponed the onset of esophagitis.

Frequency and Predictors of Acute Hospitalization Before Death in Patients With Glioblastoma.

CONTEXT: Glioblastoma (GBM) is a devastating and incurable neuro-oncologic disease, and issues related to the end of life are almost invariably a matter of "when," not a matter of "if." Optimizing symptom management and quality of life in later stages of disease is of the utmost priority. OBJECTIVES: To examine the frequency of and factors associated with late acute hospital admission before death in patients with GBM. METHODS: Case-control study comparing patients with GBM admitted to the hospital within one month of death to those without late hospital admission. RESULTS: Of 385 GBM patients followed to death at Memorial Sloan Kettering Cancer Center, 164 (42.6%) were admitted within a month of death, most frequently (140, or 85%) to manage neurologic decline. Of these, 56 (34%) had intensive care unit care during this admission and 22 (13%), 18 (11%), and 2 (1%) received mechanical ventilation, enteral feeding tubes, or cardiopulmonary resuscitation, respectively. In multivariable analysis, in-hospital chaplaincy consultation, and participation in a therapeutic clinical trial, both at any time in the GBM disease course, were significantly associated with late hospital admission. CONCLUSIONS: Late hospitalization is frequent in GBM and often involves intensive care unit care in the management of clinical events that are part of the GBM dying process. Patients with a tendency to use religious support and those enrolled in clinical trials may be at greater risk for late hospitalization. Dedicated prospective study is needed to determine predictors of late hospitalization and to examine the impact of late acute medical care on quality of life in GBM.