Esophageal Cancer Outcomes After Definitive Chemotherapy With Intensity Modulated Proton Therapy.

Purpose: The effectiveness of intensity-modulated proton therapy (IMPT) for esophageal cancer treated with definitive concurrent chemoradiation therapy remains inadequately explored. We investigated long-term outcomes and toxicity experienced by patients who received IMPT as part of definitive esophageal cancer treatment. Patients and Methods: We retrospectively identified and analyzed 34 patients with locally advanced esophageal cancer who received IMPT with concurrent chemotherapy as a definitive treatment regimen at The University of Texas MD Anderson Cancer Center from 2011 to 2021. The median IMPT dose was 50.4 GyRBE in 28 fractions; concurrent chemotherapy consisted of fluorouracil and/or taxane and/or platinum. Survival outcomes were determined by the Kaplan-Meier method, and toxicity was scored according to the Common Terminology Criteria for Adverse Events version 4.0. Results: The median age of all patients was 71.5 years. Most patients had stage III (cT3 cM0) adenocarcinoma of the lower esophagus. At a median follow-up time of 39 months, the 5-year overall survival rate was 41.1%; progression-free survival, 34.6%; local regional recurrence-free survival, 78.1%; and distant metastasis-free survival, 65.0%. Common acute chemoradiation therapy-related toxicities included hematologic toxicity, esophagitis (and late-onset), fatigue, weight loss, and nausea (and late-onset); grade 3 toxicity rates were 26.0% for hematologic, 18.0% for esophagitis and 9.0% for nausea. No patient had grade ≥3 wt loss or radiation pneumonitis, and no patients had pulmonary fibrosis or esophageal fistula. No grade ≥4 events were observed except for hematologic toxicity (lymphopenia) in 2 patients. Conclusion: Long-term survival and toxicity were excellent after IMPT for locally advanced esophageal cancer treated definitively with concurrent chemoradiation therapy. When available, IMPT should be offered to such patients to minimize treatment-related cardiopulmonary toxicity without sacrificing outcomes.

Comparing 90-Day Postoperative Mortality After Neoadjuvant Proton-Based Versus Photon-Based Chemoradiotherapy for Esophageal Cancer.

Purpose: Evidence suggests that proton-beam therapy (PBT) results in less toxicity and postoperative complications compared to photon-based radiotherapy in patients who receive chemoradiotherapy followed by esophagectomy for cancer. Ninety-day mortality (90DM) is an important measure of the postoperative (nononcologic) outcome as proxy of quality-of-care. We hypothesize that PBT could reduce 90DM compared to photon-based radiotherapy. Materials and Methods: From a single-center retrospective database patients treated with chemoradiotherapy before esophagectomy for cancer were selected (1998-2022). Univariable logistic regression was used to study the association of radiotherapy modality with 90DM. Three separate methods were applied to adjust for confounding bias, including multivariable logistic regression, propensity score matching, and inverse probability of treatment weighting. Stratified analysis for the age threshold that maximized the difference in 90DM (ie, ≥67 vs <67 years) was performed. Results: A total of 894 eligible patients were included and 90DM was 5/202 (2.5%) in the PBT versus 29/692 (4.2%) in the photon-based radiotherapy group (P = .262). After adjustment for age and tumor location, PBT versus photon-based radiotherapy was not significantly associated with 90DM (P = .491). The 90DM was not significantly different for PBT versus photon-based radiotherapy in the propensity score matching (P = .379) and inverse probability of treatment weighting cohort (P = .426). The stratified analysis revealed that in patients aged ≥67 years, PBT was associated with decreased 90DM (1.3% vs 8.8%; P = .026). Higher age significantly increased 90DM risk within the photon-based radiotherapy (8.8% vs 2.7%; P = .001), but not within the PBT group (1.3% vs 3.2%; P = .651). Conclusion: No statistically significant difference was observed in postoperative 90DM after esophagectomy for cancer between PBT and photon-based neoadjuvant chemoradiotherapy. However, among older patients a signal was observed that PBT may reduce 90DM risk.

Feasibility and first results of the 'Trials-within-Cohorts' (TwiCs) design in patients undergoing radiotherapy for lung cancer.

Background: 'Trials-within-Cohorts' (TwiCs), previously known as 'cohort multiple randomized controlled trials' is a pragmatic trial design, supporting an efficient and representative recruitment of patients for (future) trials. To our knowledge, the 'COhort for Lung cancer Outcome Reporting and trial inclusion' (COLOR) is the first TwiCs in lung cancer patients. In this study we aimed to assess the feasibility and first year results of COLOR.Material and Methods: All patients diagnosed with lung cancer referred to the Radiotherapy department were eligible to participate in the ongoing prospective COLOR study. At inclusion, written informed consent was requested for use of patient data, participation in patient-reported outcomes (PROs), and willingness to participate in (future) trials. Feasibility was studied by assessing participation and comparing baseline PROs to EORTC reference values. First-year results of PROs at baseline and 3 months after inclusion were evaluated separately for stereotactic body radiotherapy (SBRT) and conventional radiotherapy patients.Results: Of the 338 eligible patients between July 2020 and July 2021, 169 (50%) participated. Among these, 127 (75%) gave informed consent to PROs participation and 110 (65%) were willing to participate in (future) trials. The inclusion percentage dropped from 77% to 33% when the information procedure was switched from in-person to by phone (due to COVID-19 pandemic measures). Baseline PROs for physical and cognitive functioning were comparable in COLOR patients compared to the EORTC reference values. No significant changes in PROs were observed 3 months after inclusion, except for a slight increase in pain scores in the SBRT group (n = 97).Conclusions: The TwiCs-design appears feasible in lung cancer patients with fair participation rates (although negatively impacted by the COVID-19 pandemic). With a planned expansion to other centers, the COLOR-study is expected to enable multiple (randomized) evaluations of experimental interventions with important advantages for recruitment, generalizability, and long-term outcome data collection.

Long-term Local Control and Overall Survival After Radiotherapy in Oligoprogressive Patients During Treatment With Checkpoint Inhibitors.

BACKGROUND/AIM: Recent studies described the safety and clinical utility of combined anti-programmed cell death protein-1 (anti-PD1) checkpoint inhibition with radiotherapy. However, long-term follow-up data are lacking. Abscopal effects have been hypothesized, though clinical proof is still scarce. PATIENTS AND METHODS: We analyzed the efficacy and toxicity of combined (stereotactic) radiotherapy and anti-PD1 in consecutive oligoprogressive melanoma and non-small cell lung cancer (NSCLC) patients who were irradiated for 1 to 3 progressive metastases during anti-PD-1 in our institute between January 2017 and January 2019 and verified one-dimensional RECIST measurements by volumetric assessments. RESULTS: Out of 361 patients, 11 melanoma and 5 NSCLC patients were included in this series. Radiotherapy was applied after a median of 11 months (range=1-30 months) from the start of anti-PD1 treatment. No increased risk of adverse events for the combined treatments was observed. With a median follow-up of 4.9 years since the start of anti-PD1, 69% of patients were alive. Six of 16 patients had stable disease after a median follow-up of 4.1 years after radiotherapy. Abscopal effects were suspected in three out of 16 patients. However, if volumetric assessment was used, two of these patients already had tumor shrinkage prior to radiotherapy, not detected by one-dimensional measurements. CONCLUSION: Stereotactic radiotherapy for oligoprogressive disease during PD1-inhibition can induce long-term disease control. Although abscopal effects were suspected in three patients, they were not confirmed with volumetric assessment in two patients. The discrepancy found between one-dimensional and volumetric response assessment argues for including volumetric assessment in further studies.

WHO grade I meningiomas that show regrowth after gamma knife radiosurgery often show 1p36 loss.

WHO grade I meningiomas occasionally show regrowth after radiosurgical treatment, which cannot be predicted by clinical features. There is increasing evidence that certain biomarkers are associated with regrowth of meningiomas. The aim of this retrospective study was to asses if these biomarkers could be of value to predict regrowth of WHO grade I meningiomas after additive radiosurgery. Forty-four patients with WHO grade I meningiomas who underwent additive radiosurgical treatment between 2002 and 2015 after Simpson IV resection were included in this study, of which 8 showed regrowth. Median follow-up time was 64 months (range 24-137 months). Tumors were analyzed for the proliferation marker Ki-67 by immunohistochemistry and for deletion of 1p36 by fluorescence in situ hybridization (FISH). Furthermore, genomic DNA was analyzed for promoter hypermethylation of the genes NDRG1-4, SFRP1, HOXA9 and MGMT. Comparison of meningiomas with and without regrowth after radiosurgery revealed that loss of 1p36 (p = 0.001) and hypermethylation of NDRG1 (p = 0.046) were correlated with regrowth free survival. Loss of 1p36 was the only parameter that was significantly associated with meningioma regrowth after multivariate analysis (p = 0.01). Assessment of 1p36 loss in tumor tissue prior to radiosurgery might be considered an indicator of prognosis/regrowth. However, this finding has to be validated in an independent larger set of tumors.

The Influence of Severe Radiation-Induced Lymphopenia on Overall Survival in Solid Tumors: A Systematic Review and Meta-Analysis.

PURPOSE: Emerging evidence suggests a detrimental prognostic association between radiation-induced lymphopenia (RIL) and pathologic response, progression-free survival, and overall survival (OS) in patients who undergo radiation therapy for cancer. The aim of this study was to systematically review and meta-analyze the prognostic impact of RIL on OS in patients with solid tumors. METHODS AND MATERIALS: PubMed/MEDLINE and Embase were systematically searched. The analysis included intervention and prognostic studies that reported on the prognostic relationship between RIL and survival in patients with solid tumors. An overall pooled adjusted hazard ratio (aHR) was calculated using a random-effects model. Subgroup analyses for different patient-, tumor-, treatment-, and study-related characteristics were performed using meta-regression. RESULTS: Pooling of 21 cohorts within 20 eligible studies demonstrated a statistically significant association between OS and grade ≥3 versus grade 0-2 RIL (n = 16; pooled aHR, 1.65; 95% confidence interval [CI], 1.43-1.90) and grade 4 RIL versus grade 0-3 (n = 5; aHR, 1.53; 95% CI, 1.24-1.90). Moderate heterogeneity among aHRs was observed, mostly attributable to overestimated aHRs in 7 studies likely subject to model-overfitting. Subgroup analysis showed significant prognostic impact of grade ≥3 RIL in 4 brain tumor (aHR, 1.63; 95% CI, 1.06-2.51), 4 lung cancer (aHR, 1.52; 95% CI, 1.01-2.29), and 3 pancreatic cancer (aHR, 1.92; 95% CI, 1.10-3.36) cohorts. CONCLUSIONS: This meta-analysis demonstrates a significant detrimental prognostic association between grade ≥3 lymphopenia and OS in patients receiving radiation therapy for solid tumors. This finding appears consistent for tumors of the brain, thorax, and upper abdomen and provides an imperative to further elucidate the potential survival benefit of lymphopenia-mitigating strategies.