Role of Metastatic Site Irradiation in Pediatric Patients With Metastatic Ewing Sarcoma.

BACKGROUND: The use of radiation therapy to treat metastases in patients with metastatic Ewing sarcoma (MES) has been controversial and variable. The authors report outcomes and patterns of failure after metastatic site irradiation (MSI). PROCEDURE: A total of 27 pediatric patients with MES were treated with chemotherapy and received radiation therapy to their primary site. Ten patients additionally received MSI, which consisted of whole-lung irradiation (WLI) in patients with lung metastases. Metastatic sites were followed from diagnosis to the first relapse. RESULTS: Median follow-up was 29 months. Seventy-eight percent of patients relapsed. Two-year progression-free survival (PFS) and overall survival with and without MSI were 30 versus 29% (log rank P=0.38) and 60 versus 70% (log rank P=0.11), respectively. The median time to relapse among patients who relapsed was 19.5 versus 12.3 months for those receiving MSI versus those who did not (P=0.04).Seven of 20 (35%) patients with lung metastases received WLI±other MSI. Two-year PFS with and without MSI was 43% versus 23% (log rank P=0.02). Among patients with a complete response to computed tomography, 5 of 14 (36%) patients received MSI. Two-year PFS with and without MSI was 60% versus 33% (log rank P=0.04).In the cohort of patients who relapsed, among all metastatic sites at diagnosis, the disease recurred at 15% of irradiated sites and 31% of unirradiated sites. On logistic regression, no factors were statistically associated with increased risk of recurrence at initial sites of metastases. CONCLUSIONS: Relapses frequently occur at sites of prior unirradiated disease in patients with MES. WLI may improve 2-year PFS, regardless of chemotherapy response. Further investigation of the role of MSI is warranted.

Emerging role of immunotherapy in locally advanced non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) accounts for 85% of the cases of lung cancer in the United States, and 70% of patients with NSCLC have locally advanced or metastatic disease at the time of diagnosis. The 5-year overall survival rate for patients with locally advanced NSCLC is 15% to 20%. The traditional treatment paradigm for unresectable locally advanced NSCLC consists of platinum-based chemotherapy with concurrent radiation. Evidence from phase 3 clinical trials has established a role for immunotherapy after chemoradiation, and emerging data continue to elucidate the expanding role of immunotherapy.

Tumor bed proton irradiation in young children with localized medulloblastoma.

BACKGROUND: Radiotherapy is often deferred in very young children with medulloblastoma, in favor of more intense chemotherapy and stem cell rescue; however, posterior fossa radiation has been shown to improve overall survival (OS) and event-free survival compared with adjuvant chemotherapy alone. This study was performed to assess the OS, recurrence-free survival (RFS), patterns of failure, and clinical toxicity for children aged five and under who received focal proton radiation to the tumor bed alone. PROCEDURE: From 2010 to 2017, 14 patients with newly diagnosed medulloblastoma at one institution received tumor bed irradiation following surgery and chemotherapy. The median age of the patients was 40 months (range, 10.9-62.9 months). RESULTS: With a median follow-up of 54 months, four patients relapsed: three within the central nervous system (CNS) outside of the posterior fossa, and one within the tumor bed after subtotal resection. All relapses occurred within 28 months after the completion of radiation therapy. Five-year OS and RFS for this cohort of patients were 84% (95% CI, 48%-96%) and 70% (95% CI, 38%-88%), respectively. One patient experienced significant tumor regrowth soon after completion of radiation, autopsy showed viable tumor and necrosis near and within the brainstem, with relation to radiation unknown; however, no other acute clinical toxicities greater than grade 2 were observed in this group of patients. In the nine patients with available performance status follow-up, no significant changes in Lansky performance status were observed. CONCLUSIONS: Five-year OS and RFS following tumor bed irradiation in young children with medulloblastoma appear to be improved compared with other studies that forego the use of radiation therapy in this patient population. This approach should be further investigated in young children with medulloblastoma.

The Use of Lidocaine Containing Cardioplegia in Surgery for Adult Acquired Heart Disease.

BACKGROUND: Del Nido cardioplegia, a crystalloid-based solution with lidocaine as a key element, is given as a single dose and has been used successfully in congenital cardiac surgery. HYPOTHESIS: We retrospectively compared a lidocaine containing "modified del Nido" solution with our standard whole blood cardioplegia to investigate its safety and efficacy in adult cardiac surgery. METHODS: From June 1, 2013 to December 30, 2013, we used a single dose of lidocaine containing cardioplegia (LC group) in 92 consecutive operations. Propensity matching analysis was undertaken to compare the outcomes of such patients with those who underwent their surgery by the same surgeon using standard whole blood cardioplegia (WB group), n = 396. Propensity score matching yielded 79 pairs of patients. RESULTS: After propensity matching, LC and WB groups were similar in baseline operative characteristics including cross-clamp time (LC: 65 minutes [range 54 to 89] vs. WB: 70 minutes [54 to 86], p = 0.993). Postoperative outcomes were similar including inotropic requirements (30.4% [24/72] vs. 25.3% [20/72], p < 0.60), median ventilation time (4.7 hours vs. 5.3, p < 0.74) and median length of stay was seven days for both groups (p < 0.82). Despite higher median postoperative, 24-hour CK-MB levels LC group (LC:22.3 ng/ml, range [15.6 to 40.3] vs. WB:18.4 ng/ml [13.9 to 28.2], p = 0.040), operative and one-year mortality were comparable among study groups (both p > 0.798). CONCLUSIONS: Lidocaine containing cardioplegia appears to be safe in adults undergoing cardiac procedure when administered for the first 60 minutes of aortic cross clamping. Higher CK-MB levels did not translate into adverse clinical outcomes.

Activity Monitoring for Toxicity Detection and Management in Patients Undergoing Chemoradiation for Gastrointestinal Malignancies.

PURPOSE: Physical activity is associated with decreased hospitalization during cancer treatment. We hypothesize that activity data can help identify and triage high-risk patients with GI cancer undergoing concurrent chemoradiation. MATERIALS AND METHODS: This prospective study randomly assigned patients to activity monitoring versus observation. In the intervention arm, a 20% decrease in daily steps or 20% increase in heart rate triggered triage visits to provide supportive care, medication changes, and escalation of care. In the observation group, activity data were recorded but not monitored. The primary objective was to show a 20% increase in triage visits in the intervention group. Secondary objectives were estimating the rates of emergency department (ED) visits and hospitalizations. Crude and adjusted odds ratios were computed using logistic regression modeling. RESULTS: There were 22 patients in the intervention and 18 in the observation group. Baseline patient and treatment characteristics were similar. The primary objective was met, with 3.4 more triage visits in the intervention group than in the observation group (95% CI, 2.10 to 5.50; P < .0001). Twenty-six (65.0%) patients required at least one triage visit, with a higher rate in the intervention arm compared with that in the observation arm (86.4% v 38.9%; odds ratio, 9.95; 95% CI, 2.13 to 46.56; P = .004). There was no statistically significant difference in ED visit (9.1% v 22.2%; P = .38) or hospitalization (4.5% v 16.7%; P = .31). CONCLUSION: It is feasible to use activity data to trigger triage visits for symptom management. Further studies are investigating whether automated activity monitoring can assist with early outpatient management to decrease ED visits and hospitalizations.

A Pooled Toxicity Analysis of Moderately Hypofractionated Proton Beam Therapy and Intensity Modulated Radiation Therapy in Early-Stage Prostate Cancer Patients.

PURPOSE: Data comparing moderately hypofractionated intensity modulated radiation therapy (IMRT) and proton beam therapy (PBT) are lacking. We aim to compare late toxicity profiles of patients with early-stage prostate cancer treated with moderately hypofractionated PBT and IMRT. METHODS AND MATERIALS: This multi-institutional analysis included patients with low- or intermediate-risk biopsy-proven prostate adenocarcinoma from 7 tertiary referral centers treated from 1998 to 2018. All patients were treated with moderately hypofractionated radiation, defined as 250 to 300 cGy per daily fraction given for 4 to 6 weeks, and stratified by use of IMRT or PBT. Primary outcomes were late genitourinary (GU) and gastrointestinal (GI) toxicity. Adjusted toxicity rates were calculated using inverse probability of treatment weighting, accounting for race, National Comprehensive Cancer Network risk group, age, pretreatment International Prostate Symptom Score (GU only), and anticoagulant use (GI only). RESULTS: A total of 1850 patients were included: 1282 IMRT (median follow-up 80.0 months) and 568 PBT (median follow-up 43.9 months). Overall toxicity rates were low, with the majority of patients experiencing no late GU (56.6%, n = 1048) or late GI (74.4%, n = 1377) toxicity. No difference was seen in the rates of late toxicity between the groups, with late grade 3+ GU toxicity of 2.0% versus 3.9% (odds ratio [OR] 0.47; 95% confidence interval 0.17-1.28) and late grade 2+ GI toxicity of 14.6% versus 4.7% (OR 2.69; confidence interval 0.80-9.05) for the PBT and IMRT cohorts, respectively. On multivariable analysis, no factors were significantly predictive of GU toxicity, and only anticoagulant use was significantly predictive of GI toxicity (OR 1.90; P = .008). CONCLUSIONS: In this large, multi-institutional analysis of 1850 patients with early-stage prostate cancer, treatment with moderately hypofractionated IMRT and PBT resulted in low rates of toxicity. No difference was seen in late GI and GU toxicity between the modalities during long-term follow-up. Both treatments are safe and well tolerated.

Pharyngeal-sparing radiation for head and neck carcinoma of unknown primary following TORS assisted work-up.

OBJECTIVE: In patients with head and neck carcinoma of unknown primary (HNCUP;pT0) following TORS-assisted workup, we have adopted a pharyngeal-sparing radiation therapy (PSRT) approach targeting only the at-risk neck and omitting treatment of the pharynx. We report outcomes following PSRT, and compare to institutional historical control subjects who received pharyngeal-targeted RT (PRT). METHODS: Between 2009 and 2018, 172 patients underwent TORS-assisted endoscopy as part of their workup for HNCUP. Following TORS, 54 patients had pT0 disease, of which 45 received RT. Forty-nine percent received PSRT and 51% received PRT. RESULTS: No statistically significant differences existed between the PSRT and PRT groups with respect to overall nodal distribution, p16 positivity (55% vs. 43%, P = .12), neck dissection rates (77% vs. 65%, P = .51), and administration of chemotherapy (55% vs. 65%, P = .55). Median follow-up for PSRT and PRT groups were 24 and 28 months, respectively (P = .04). Two-year RFS was 86% and 74% for PSRT and PRT patients, respectively (log-rank P = .30). Three and six patients recurred after PSRT and PRT, respectively. Two-year OS for PSRT and PRT patients was 91% and 74%, respectively (log-rank P = .31). Compared to PRT, PSRT was associated with statistically significantly less: grade 2+ mucositis (18% vs. 91%, P < .01), new opioid requirement (27% vs. 91%, P < .01), mean weight loss during RT (6.2 lbs vs. 17.4 lbs, P < .01), feeding tube placement during RT (5% vs. 43%, P < .01), and treatment-related unplanned hospitalizations (9% vs. 39%, P = .04). CONCLUSION: Following TORS-assisted management of patients with pT0 HNCUP, we observed reduced toxicity following PSRT compared to PRT without apparent compromise of disease cure. LEVEL OF EVIDENCE: Level 3 evidence, retrospective review comparing cases and controls Laryngoscope, 130:691-697, 2020.

Early Tumor and Nodal Response in Patients with Locally Advanced Non-Small Cell Lung Carcinoma Predict for Oncologic Outcomes in Patients Treated with Concurrent Proton Therapy and Chemotherapy.

PURPOSE: There are no established imaging biomarkers that predict response during chemoradiation for patients with locally advanced non-small cell lung carcinoma. At our institution, proton therapy (PT) patients undergo repeat computed tomography (CT) simulations twice during radiation. We hypothesized that tumor regression measured on these scans would separate early and late responders and that early response would translate into better outcomes. METHODS AND MATERIALS: Patients underwent CT simulations before starting PT (CT0) and between weeks 1 to 3 (CT1) and weeks 4 to 7 (CT2) of PT. Primary tumor volume (TVR) and nodal volume (NVR) reduction were calculated at CT1 and CT2. Based on recursive partitioning analysis, early response at CT1 and CT2 was defined as ≥20% and ≥40%, respectively. Locoregional and overall progression-free survival (PFS), distant metastasis-free survival, and overall survival by response status were measured using Kaplan-Meier analysis. RESULTS: Ninety-seven patients with locally advanced non-small cell lung carcinoma underwent definitive PT to a median dose of 66.6 Gy with concurrent chemotherapy. Median TVR and NVR at CT1 were 19% (0-79%) and 19% (0-75%), respectively. At CT2, they were 33% (2-98%) and 35% (0-89%), respectively. With a median follow-up of 25 months, the median overall survival and PFS for the entire cohort was 24.9 and 13.2 months, respectively. Compared with patients with TVR and NVR <20% at T1 and <40% at T2, patients with TVR and NVR ≥20% at CT1 and ≥40% at CT2 had improved median locoregional PFS (27.15 vs 12.97 months for TVR ≥40% vs <40%, P < .01, and 25.67 vs 12.09 months for NVR ≥40% vs <40%, P < .01) and median PFS (22.7 vs 9.2 months, P < .01, and 20.3 vs 7.9 months, P < .01), confirmed on multivariate Cox regression analysis. CONCLUSIONS: Significantly improved outcomes in patients with early responses to therapy, as measured by TVR and NVR, were seen. Further study is warranted to determine whether treatment intensification will improve outcomes in slow-responding patients.

Palliative Radiation Therapy for Head and Neck Cancers.

Patients with advanced head and neck cancers who are not eligible for curative treatment represent a challenging cohort of patients to manage given the complexity and severity of their presenting symptoms. Palliative radiation therapy, along with other systemic and surgical measures, has the potential to significantly improve the quality of life of such patients. There is little high-level evidence and a lack of consensus to direct the selection of an optimal palliative radiation regimen. An ideal palliative radiation regimen should alleviate symptoms secondary to the cancer with minimal treatment toxicity and side effects while improving a patient's quality of life. This review presents the treatment approaches, outcomes, and toxicities associated with different radiation regimens and proposes a multidisciplinary framework for the selection of an individualized treatment regimen for patients that centers around patient prognosis, goals of care, logistics of treatment, and the availability of other surgical and systemic therapies.

Patient-Centered Outcomes in Radiation Oncology.

Patient-reported outcome and health-related quality of life scales have the potential to engage patients and providers, allowing for better communication and shared decision-making in oncology care. When monitored longitudinally, they facilitate earlier interventions that may help with symptom management and improve traditional outcome metrics, including survival. Their use in clinical trials has allowed for changes in guidelines in the management of various cancers. The voice and experience of the patient, captured by these scales, enable providers to better detail the journey patients can expect to experience during and after treatment.

Four-Year Outcomes From a Prospective Phase II Clinical Trial of Moderately Hypofractionated Proton Therapy for Localized Prostate Cancer.

PURPOSE: Moderately hypofractionated radiation therapy represents an effective treatment for localized prostate cancer (PC). Although large randomized trials have reported the efficacy of photon-based hypofractionated therapy, hypofractionated proton therapy (HFPT) has not been extensively studied. This study was performed to determine the clinical and patient-reported outcomes for patients with PC treated with HFPT. METHODS AND MATERIALS: Between 2010 and 2017, 184 men were enrolled on a trial of 70 Gy in 28 fractions of HFPT for low- to intermediate-risk PC. Acute and late toxicity was evaluated using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Patient-reported outcomes were measured by International Prostate Symptom Score, International Index of Erectile Function Questionnaire, and Expanded Prostate Cancer Index Composite scores. RESULTS: Median follow-up was 49.2 months. Enrolled patients had low-risk (n = 18), favorable intermediate-risk (n = 78), and unfavorable intermediate-risk (n = 88) PC. Four-year rates of biochemical-clinical failure-free survival were 93.5% (95% confidence interval, 89%-98%), 94.4% (89%-100%), 92.5% (86%-100%), and 93.8% (88%-100%) in the overall group and the low-risk, favorable intermediate-risk, and unfavorable intermediate-risk cohorts, respectively (log-rank P > .4). The incidence of acute grade 2 or higher gastrointestinal (GI) and urologic toxicities were 3.8% and 12.5%, respectively. The 4-year incidence of late grade 2 or higher urologic and GI toxicity was 7.6% (4%-13%) and 13.6% (9%-20%), respectively. One late grade 3 GI toxicity was reported. All late toxicities were transient. Patient-reported International Prostate Symptom, International Index of Erectile Function, and Expanded Prostate Cancer Index Composite scores had no significant long-term changes after completion of HFPT (Supplementary Table 1, available at https://doi.org/10.1016/j.ijrobp.2019.05.069). CONCLUSIONS: HFPT is associated with low rates of toxicity and does not appear to negatively affect 4-year patient reported urinary and bowel health. Further comparative analyses are warranted to better understand differences between proton and photon HFRT.

Prevalence and outcome of lung cancer in lung transplant recipients.

BACKGROUND: Lung transplant is the only available therapy for patients with advanced lung disease. The goal of this study was to examine the prevalence, origin, management and outcome of lung cancer in recipients of lung transplant at our institution. METHODS: After institutional review board approval, we conducted a retrospective chart review of all lung transplantations in our institution from January 1990 until June 2012. RESULTS: The prevalence of lung cancer in the explanted lung was 6 (1.2%) of 462 and all cases were in subjects with lung fibrosis. All 4 subjects with lymph node involvement died of causes related to the malignancy. Nine (1.9%) of 462 patients were found to have bronchogenic carcinoma after lung transplant. The most common location was in the native lung in recipients of a single lung transplant (6 out of 9 patients). In one case, the tumor originated in the allograft and was potentially donor related. The median time to diagnosis after lung transplant was 28 months with a range from 9 months to 10 years. Median survival was 8 months, with tumors involving lymph nodes or distant metastases associated with a markedly worse prognosis (median survival 7 months) than stage I disease (median survival 27 months). CONCLUSIONS: The prevalence of lung cancer in lung transplant recipients is low. Using accepted donor screening criteria, donor derived malignancy is exceptionally rare. While stage I disease is associated with improved survival in this cohort, survival is still not comparable to that of the general population, likely influenced by the need for aggressive immune suppression.