Acute adverse events of ultra-hypofractionated whole-breast irradiation after breast-conserving surgery for early breast cancer in Japan: an interim analysis of the multi-institutional phase II UPBEAT study.

BACKGROUND: The applicability of ultra-hypofractionated (ultra-HF) whole-breast irradiation (WBI) remains unknown in Japanese women. This study aimed to evaluate the safety and efficacy of this approach among Japanese women and report the results of an interim analysis performed to assess acute adverse events (AEs) and determine whether it was safe to continue this study. METHODS: We enrolled Japanese women with invasive breast cancer or ductal carcinoma in situ who had undergone breast-conserving surgery, were aged ≥ 40 years, had pathological stages of Tis-T3 N0-N1, and had negative surgical margins. Ultra-HF-WBI was delivered at 26 Gy in five fractions over one week. When the number of enrolled patients reached 28, patient registration was paused for three months. The endpoint of the interim analysis was the proportion of acute AEs of grade ≥ 2 (Common Terminology Criteria for Adverse Events v5.0) within three months. RESULTS: Of the 28 patients enrolled from seven institutes, 26 received ultra-HF-WBI, and 2 were excluded due to postoperative infections. No AEs of grade ≥ 3 occurred. One patient (4%) experienced grade 2 radiation dermatitis, and 18 (69%) had grade 1 radiation dermatitis. The other acute grade 1 AEs experienced were skin hyperpigmentation (n = 10, 38%); breast pain (n = 4, 15%); superficial soft tissue fibrosis (n = 3, 12%); and fatigue (n = 1, 4%). No other acute AEs of grade ≥ 2 were detected. CONCLUSIONS: Acute AEs following ultra-HF-WBI were within acceptable limits among Japanese women, indicating that the continuation of the study was appropriate.

Recurrence patterns and progression-free survival after chemoradiotherapy with or without consolidation durvalumab for stage III non-small cell lung cancer.

Chemoradiotherapy followed by consolidation durvalumab (CCRT+D) improves survival in patients with stage III non-small-cell lung cancer (NSCLC). We compared recurrence patterns and survival in the CCRT+D and CCRT cohorts. We conducted a multicenter, retrospective study in Japan. Patients who received CCRT for stage III NSCLC were included in this study. Of 178 eligible patients, 136 were in the CCRT+D and 42 were in the CCRT cohorts. Locoregional recurrence (LR), LR plus distant metastases (DM), and DM were observed in 20.6%, 8.8%, 27.9% of the CCRT+D, and 26.2%, 16.7% and 33.3% of the CCRT cohorts, respectively. In-field recurrence was the most common LR pattern in both cohorts. Squamous cell carcinoma and PD-L1 expression < 1%, and female sex and EGFR mutations were significantly associated with an increased risk of LR and DM. In patients with any risk factors for LR, the incidence of LR was similar in the CCRT+D and CCRT (39.5% vs 45.5%). The 24 month progression-free survival (PFS) and overall survival (OS) were 40.3% and 69.4% in the CCRT+D and 24.7% and 61.0% in the CCRT cohorts, respectively. Poor performance status and no consolidation durvalumab were significantly associated with shorter PFS. There was a significant difference in PFS between the CCRT+D and CCRT in the propensity score-matched cohort (HR = 0.51, P = 0.005). In conclusion, consolidation durvalumab decreased both LR and DM, and significantly improved PFS. However, in-field recurrence was still a major problem, as well as DM.

Incidence and Risk Factors of Symptomatic Radiation Pneumonitis in Non-Small-Cell Lung Cancer Patients Treated with Concurrent Chemoradiotherapy and Consolidation Durvalumab.

INTRODUCTION: Data on the risk factors for symptomatic radiation pneumonitis (RP) in non-small-cell lung cancer (NSCLC) patients treated with concurrent chemoradiotherapy (CCRT) and consolidation durvalumab are limited; we aimed to investigate these risk factors. MATERIALS AND METHODS: This multicenter retrospective study, conducted at 15 institutions in Japan, included patients who were ≥20 years of age; who started definitive CCRT for NSCLC between July 1, 2018, and July 31, 2019; and who then received durvalumab. The primary endpoint was grade 2 or worse (grade 2+) RP. RESULTS: In the 146 patients analyzed, the median follow-up period was 16 months. A majority of the patients had stage III disease (86%), received radiation doses of 60 to 66 Gy equivalent in 2-Gy fractions (93%) and carboplatin and paclitaxel/nab-paclitaxel (77%), and underwent elective nodal irradiation (71%) and 3-dimensional conformal radiotherapy (75%). RP grade 2 was observed in 44 patients (30%); grade 3, in four patients (3%); grade 4, in one patient (1%); and grade 5, in one patient (1%). In the multivariable analysis, lung V20 was a significant risk factor, whereas age, sex, smoking history, irradiation technique, and chemotherapy regimen were not. The 12-month grade 2+ RP incidence was 34.4% (95% confidence interval [CI], 26.7%-42.1%); the values were 50.0% (95% CI, 34.7%-63.5%) and 27.1% (95% CI, 18.8%-36.2%) in those with lung V20 ≥ 26% and < 26%, respectively (P = .007). CONCLUSION: The incidence of grade 2+ RP was relatively high in this multicenter real-world study, and its risk increased remarkably at elevated lung V20. Our findings can aid in RP risk prediction and the safe radiotherapy treatment planning.

Concurrent chemoradiotherapy for esophageal cancer: comparison between intermittent standard-dose cisplatin with 5-fluorouracil and daily low-dose cisplatin with continuous infusion of 5-fluorouracil.

BACKGROUND: Although current standard treatment for advanced esophageal cancer is intermittent standard-dose cisplatin with 5-fluorouracil (5-FU) (ISD-FP), daily low-dose cisplatin with continuous infusion of 5-FU (CLD-FP) is advocated for equivalent effectiveness and lower toxicity. The feasibility of these two concurrent chemoradiotherapeutic protocols was retrospectively reviewed for local control rate, overall survival, toxicity, and compliance in a single institutional situation. METHODS: Concurrent chemoradiotherapy, using 60 Gy of radiation and ISD-FP or CLD-FP was non-randomly scheduled for 29 patients between June 1994 and March 2001. RESULTS: Complete response in the irradiated volume at the end of primary treatment was shown by 8 of 15 and 9 of 14 patients in the ISD-FP and CLD-FP groups, respectively. The projected overall survival rate at 2 years was 55% for stage III patients and 13% for stage IV. Median survival times were 14 months versus 15 months in the ISD-FP and CLD-FP groups, with no significant difference. Toxicities were similar, including two treatment-related deaths in each group. Chemotherapy was completed for 10 of 15 and 11 of 14 patients in the ISD-FP and CLD-FP groups, respectively. Modification of the planned regimen was more often required for the CLD-FP group. CONCLUSION: CLD-FP therapy has no apparent advantage over ISD-FP therapy from the perspective of compliance and safety. A randomized phase II clinical trial comparing ISD-FP and CLD-FP, currently being performed, is expected to provide further information. Although current standard treatment for advanced esophageal cancer is intermittent standard-dose cisplatin with 5-fluorouracil (5-FU) (ISD-FP), daily low-dose cisplatin with continuous infusion of 5-FU (CLD-FP) is advocated for equivalent effectiveness and lower toxicity. The feasibility of these two concurrent chemoradiotherapeutic protocols was retrospectively reviewed for local control rate, overall survival, toxicity, and compliance in a single institutional situation.

Feasibility of breast-conserving therapy for macroscopically multiple ipsilateral breast cancer.

PURPOSE: Macroscopically multiple ipsilateral breast cancer (MMIBC) is generally considered a contraindication for breast-conserving therapy (BCT). The result of BCT for MMIBC is reported and the feasibility discussed. METHODS AND MATERIALS: Between July 1993 and February 1999, 34 patients with MMIBC underwent BCT at our clinic. The local control, disease-free survival, and cosmetic results in these patients were compared with those of patients with single disease. RESULTS: After wide excision, 21 (62%) of 34 patients with MMIBC had a close surgical margin and the rate was significantly greater than that of patients with a single lesion. However, the size of the boost irradiation field was not significantly increased. At a median follow-up of 98 months, no statistically significant difference was noted in local control, disease-free survival, or cosmetic result compared with patients with a single lesion. CONCLUSION: Although patients with MMIBC frequently had close surgical margins after BCT, it can be a treatment option for these patients as long as the close surgical margin is accurately detected and treated with an appropriate radiation technique.

Radiation therapy for brain metastases from breast cancer.

BACKGROUND: Breast cancer is one of the most common malignancies that metastasize to the brain. Radiation therapy plays a central role in the management of brain metastases. METHODS: The medical records of 36 patients with brain metastases from breast cancer who underwent whole-brain radiation therapy (WBRT) at Kyoto University Hospital between 1993 and 2001 were reviewed. The treatment outcomes were analyzed retrospectively. RESULTS: The median age at the time of diagnosis of brain metastases was 52 years. Only 4 patients (11%) had a single metastasis, while the others had multiple metastases. Uncontrolled extracranial metastases were present in 26 patients at the time of diagnosis of brain metastases. All patients received WBRT at a median dose of 31 Gy. Eight patients received conventional external-beam boost irradiation, and 2 received boost stereotactic radiosurgery (SRS). The overall median survival time was 7.9 months. Uncontrolled extracranial metastases except for bone metastases and old age were significantly associated with a poor survival rate. Twenty-six patients (82%) showed initial response, but 15 developed CNS failure, including 9 patients whose tumor recurred at the original site, 4 patients who developed tumors elsewhere in the brain and 3 patients who exhibited meningeal spread. The median duration of intracranial failure was 5.0 months. Whole-brain dose, and total tumor dose did not affect intracranial control. CONCLUSIONS: Radiation therapy yielded a high initial response, but the duration of effect was limited with external beam irradiation alone. New treatment strategies such as adding SRS need to be studied further.

Late skin and subcutaneous soft tissue changes after 10-gy boost for breast conserving therapy.

PURPOSE: To evaluate the influence of boost irradiation for breast conserving therapy on skin and subcutaneous tissue. MATERIALS AND METHODS: Between 1989 and 1995, 468 patients were treated with breast conserving surgery (quadrantectomy or wide excision with axillary dissection) followed by 50 Gy whole breast irradiation. Among them, fifty-eight patients with positive or close margins were treated with 10 Gy external beam boost irradiation. Skin and subcutaneous soft tissue changes during 5-years of follow-up were examined by inspection and palpation and evaluated using the BCT follow-up form based on EORTC late effect toxicity scoring. RESULT: Four percent (20/468) of the patients showed grade 2 late changes in skin and soft tissue. Four of them had skin telangiectasis, which was limited to within the boost field. Boost irradiation had no definite influence on other late changes. Patients' age, extent of surgery, and pT size had no significant relation to the late changes. The cosmetic score 5 years after BCT was not significantly different between the patients with and without boost irradiation. CONCLUSION: Although 10 Gy boost irradiation after 50 Gy whole breast irradiation increased skin telangiectasis, the late skin and soft tissue changes caused by the boost irradiation were generally mild and there was no substantial deterioration of cosmetic outcome.