Treatment-related pulmonary adverse events induced by chemoradiation and Durvalumab affect survival in locally advanced non-small cell lung cancer.

PURPOSE: We compared treatment-related pulmonary adverse events (TRPAE), progression-free survival (PFS), and overall survival (OS) among locally advanced non-small cell lung cancer (NSCLC) patients who received concurrent chemoradiotherapy (CRT) versus CRT followed by immune check point inhibitor (ICI) immunotherapy (CRTI). MATERIALS AND METHODS: TRPAE was defined as any pulmonary events as defined in CTCAE v.5 occurring within 12 months after completion of radiotherapy. Outcomes were compared between CRT and CTRI by Cox proportional hazard regression and Kaplan-Meier analyses. We also assessed if TRPAE-induced discontinuation of ICI affected survival. RESULTS: We analyzed 326 patients treated between July 2010 and November 2019; 195 patients received CRT and 131 received CRTI. The incidences of severe grade ≥ 3 TRPAE were similar between the two groups, however, symptomatic TRPAE was almost doubled in CRTI group (65.7 % CTRI vs 35.9 % CRT, P < 0.0001). The rates of 4-year OS and PFS were 54.5 % vs 36.7 % (P = 0.0003) and 43.8 % vs 35.8 % (P = 0.038) in CRT + Durvalumab and CRT group, respectively. Receipt of ICI Durvalumab was associated with better 4-year OS (HR 0.53, 95 % CI 0.36-0.78, P = 0.001) and PFS (HR 0.55, 95 % CI 0.38-0.80, P = 0.002). Patients who discontinued ICI because of TRPAE had worse 4-year OS (P = 0.001) and higher rates of distant metastasis (P = 0.003) than those who completed planned ICI after developing TRPAE. CONCLUSION: CRT followed by adjuvant ICI led to improved 4-year OS and PFS consistent with published data. CRTI was associated with higher incidence of grade ≥ 2 TRPAE in both high and low mean lung dose groups without significant difference in grade ≥ 3 TRPAE. Discontinuation of ICI due to TRPAE was associated with poorer OS and distant disease control than completing ICI as planned after developing TRPAE.

Proton Beam Therapy for Localized Prostate Cancer: Results from a Prospective Quality-of-Life Trial.

PURPOSE: To report prostate cancer outcomes, toxicity, and quality of life (QOL) in men treated with proton beam therapy (PBT). PATIENTS AND METHODS: Patients were enrolled in a prospective trial. All participants received 75.6 to 78 Gy (RBE). Up to 6 months of luteinizing hormone-releasing hormone agonist therapy was allowed. The Phoenix definition defined biochemical failure. Modified Radiation Therapy Oncology Group criteria defined toxicity. Expanded Prostate Cancer Index Composite questionnaires objectified QOL. Clinically significant QOL decrement was defined as ≥0.5 × baseline standard deviation. RESULTS: In total, 423 men were analyzed. The National Comprehensive Cancer Network risk classification was used (low 43%; intermediate 56%; high 1%). At the 5.2-year median follow-up, overall and disease-specific survival rates were 99.8% and 100%, respectively. Cumulative biochemical failure rate was 5.2% (95% confidence interval [CI] = 3.0%-8.3%); acute grade 2 genitourinary (GU) toxicity was 46.3%; acute grade 2 gastrointestinal (GI) toxicity was 5.0% (95% CI = 3.1%-7.3%). There was no acute grade ≥3 GI or GU toxicity. Cumulative late grade 2 GU and GI toxicity was 15.9% (95% CI = 13%-20%) and 9.7% (95% CI = 6.5%-12%), respectively. There were 2 grade 3 late GI toxicities (rectal bleeding) and no late grade ≥3 GU toxicity. The 4-year mean Expanded Prostate Cancer Index Composite urinary, bowel, sexual, and hormonal summary scores (range; standard deviation) were 89.7 (43.8-100; 11), 91.3 (41.1-94.6; 10), 57.8 (0.0-96.2; 27.1), and 92.2 (25-95.5; 10.5), respectively. Compared with baseline, there was no clinically significant decrement in urinary, sexual, or hormonal QOL after treatment completion. A modest (<10 points), yet clinically significant, decrement in bowel QOL was appreciated throughout follow-up. CONCLUSION: Contemporary PBT resulted in excellent biochemical control, minimal risk of higher-grade toxicity, and modest QOL decrement. Further investigation comparing PBT with alternative prostate cancer treatment strategies are warranted.

Quality of life and toxicity from passively scattered and spot-scanning proton beam therapy for localized prostate cancer.

PURPOSE: To report quality of life (QOL)/toxicity in men treated with proton beam therapy for localized prostate cancer and to compare outcomes between passively scattered proton therapy (PSPT) and spot-scanning proton therapy (SSPT). METHODS AND MATERIALS: Men with localized prostate cancer enrolled on a prospective QOL protocol with a minimum of 2 years' follow-up were reviewed. Comparative groups were defined by technique (PSPT vs SSPT). Patients completed Expanded Prostate Cancer Index Composite questionnaires at baseline and every 3-6 months after proton beam therapy. Clinically meaningful differences in QOL were defined as ≥0.5 × baseline standard deviation. The cumulative incidence of modified Radiation Therapy Oncology Group grade ≥2 gastrointestinal (GI) or genitourinary (GU) toxicity and argon plasma coagulation were determined by the Kaplan-Meier method. RESULTS: A total of 226 men received PSPT, and 65 received SSPT. Both PSPT and SSPT resulted in statistically significant changes in sexual, urinary, and bowel Expanded Prostate Cancer Index Composite summary scores. Only bowel summary, function, and bother resulted in clinically meaningful decrements beyond treatment completion. The decrement in bowel QOL persisted through 24-month follow-up. Cumulative grade ≥2 GU and GI toxicity at 24 months were 13.4% and 9.6%, respectively. There was 1 grade 3 GI toxicity (PSPT group) and no other grade ≥3 GI or GU toxicity. Argon plasma coagulation application was infrequent (PSPT 4.4% vs SSPT 1.5%; P=.21). No statistically significant differences were appreciated between PSPT and SSPT regarding toxicity or QOL. CONCLUSION: Both PSPT and SSPT confer low rates of grade ≥2 GI or GU toxicity, with preservation of meaningful sexual and urinary QOL at 24 months. A modest, yet clinically meaningful, decrement in bowel QOL was seen throughout follow-up. No toxicity or QOL differences between PSPT and SSPT were identified. Long-term comparative results in a larger patient cohort are warranted.

Proton beam therapy for the treatment of prostate cancer.

Proton beam therapy (PBT) offers the potential of dose escalation to target tissue while decreasing toxicity through unique physical dose deposition characteristics. PBT has been used to treat prostate cancer for several decades; however, recent enhancements in availability and treatment delivery have peaked interest in this technology among radiation oncologists, industry experts, and prostate cancer patients. As a result, the importance of understanding the collective experience and technical aspects of PBT delivery has become increasingly important in radiation medicine. This review article is intended to critically review the literature on PBT for localized prostate cancer, discuss the fundamentals of PBT treatment planning, and describe the continued development of proton beam technology for the treatment of prostate cancer.