Long-term results of hypofractionation with concomitant boost in patients with early breast cancer: A prospective study

Aim To report the long-term local control and survival of patients with early breast cancer who had hypofractionated whole breast irradiation with concomitant boost (Hypo-CB). Methods and materials Between October 2009 and June 2010, 73 patients with early breast cancer (T1-3N0-1M0) who underwent breast conserving surgery were enrolled into the study. Thirty-six of these participants received 50 Gy of conventional irradiation in 25 fractions over 5 weeks to the whole breast with a sequential boost to the tumor bed with 10–16 Gy in 5–8 fractions (Conv-SEQ). The other 37 participants received a hypofractionated dose of 43.2 Gy in 16 fractions with an additional daily concomitant boost (CB) of 0.6 Gy over 3 weeks (Hypo-CB). Results At a median follow-up time of 123 months, ipsilateral local recurrence (ILR) was found in 3 participants, 1 of whom was in the hypofractionated group. All 3 ILR were true local recurrence (TR). There were no significant differences in the 10-year disease free survival (DFS) and 10-year overall survival rates (OS) between the conventional and hypofractionated groups (93.9% vs. 94.4%, p = 0.96 and 91.9% vs. 91.6%, p = 0.792, respectively). Conclusion This study showed that the effectiveness, DFS and OS were comparable between hypofractionated whole breast irradiation with a CB and the conventional irradiation with a sequential boost.

Phase 3 comparison of high-dose once-daily (QD) thoracic radiotherapy (TRT) with standard twice-daily (BID) TRT in limited stage small cell lung cancer (LSCLC): CALGB 30610 (Alliance)/RTOG 0538.

8505 Background: Although level 1 evidence is lacking, the majority of patients (pts) with LSCLC are treated with a high dose QD TRT regimen in clinical practice. CALGB 30610/RTOG 0538 was designed to determine if administering high dose TRT would improve overall survival (OS), compared with standard 45 Gy BID TRT, in LSCLC pts treated with chemoradiotherapy. Methods: Eligible pts had LSCLC, ECOG performance status (PS) 0-2 and regional lymph node involvement excluding contralateral hilar or supraclavicular nodes. This phase 3 trial was conducted in 2 stages. In the first stage, pts were randomized 1:1:1 to 45 Gy BID over 3 weeks, 70 Gy QD over 7 weeks, or 61.2 Gy concomitant boost (CB) over 5 weeks. For the second stage, the study planned discontinuation of one high dose arm based on interim toxicity analysis with patients then randomized 1:1 in the two remaining arms. TRT was given starting with either the 1st or 2nd (of 4 total) chemotherapy cycles. The primary endpoint was OS measured from date of randomization. Results: The trial opened 03/15/2008 and closed 12/01/2019 upon completing accrual, with the CB arm discontinued 3/11/2013 after interim analysis. This analysis includes 638 pts randomized to 45 Gy BID TRT (n = 313) or 70 Gy QD TRT (n = 325). Median age was 63 years (range 37-81), the majority of pts were Caucasian (86%), female (52%), and with ECOG PS 0-1 (95%). After median follow-up of 2.84 years (IQR:1.35 -5.61) for surviving pts, QD compared to BID did not result in a significant difference in OS (HR 0.94, 95% CI: 0.76-1.2, p = 0.9). Median, 2- and 4-year OS for QD were 30.5 months (95% CI: 24.4-39.6), 56% (95% CI: 0.51-0.62), and 39% (95% CI: 0.33-0.45), and for BID 28.7 months (95% CI: 26.2-35.5), 59% (95% CI: 0.53-0.65), and 35% (95% CI: 0.29-0.42). QD also did not result in a significant difference in PFS (HR 0.96, 95% CI: 0.78-1.18, p = 0.94). Most grade 3+ hematologic and non-hematologic adverse events (AEs) were similar between cohorts. Rates of grade 3+ febrile neutropenia, dyspnea, esophageal pain and dysphagia for QD were 12.6%,7%, 11.6% and 11.3%, and for BID 13.6%, 4%, 11.2 % and 9.5%. Grade 5 AEs were reported in 3.7% and 1.7% of the QD and BID cohorts, respectively. Results will be updated at presentation. Conclusions: High dose QD TRT to 70 Gy did not significantly improve OS compared with standard 45 Gy BID TRT. Nevertheless, favorable outcomes on the QD arm provide the most robust evidence available supporting high dose once-daily TRT as an acceptable option in LSCLC. Outcomes from this study, the largest conducted in LSCLC to date, will help guide TRT decisions for this patient population. Support: U10CA180821, U10CA180882; Clinical trial information: NCT00632853.

Salvage Radiotherapy for Macroscopic Local Recurrence Following Radical Prostatectomy

IntroductionSalvage radiotherapy is the only curative treatment for biochemical progression after radical prostatectomy. Macroscopic recurrence may be found in the prostatic bed. The purpose of our study is to evaluate the effectiveness of salvage radiotherapy of the prostate bed with a boost to the area of the macroscopic recurrence.Material and MethodsFrom January 2005 to January 2020, 89 patients with macroscopic recurrence in the prostatectomy bed were treated with salvage radiotherapy +/- hormone therapy. The average PSA level prior to radiotherapy was 1.1 ng/mL (SD: 1.6). At the time of biochemical progression, 96% of the patients had a MRI that revealed the macroscopic recurrence, and 58% had an additional choline PET scan. 67.4% of the patients got a boost to the macroscopic nodule, while 32.5% of the patients only underwent radiotherapy of the prostate bed without a boost. The median total dose of radiotherapy was 70 Gy (Min.: 60 – Max.: 74). The most commonly-used regimen was radiotherapy of the prostatectomy bed with a concomitant boost. 48% of the patients were concomitantly treated with hormone therapy.ResultsAfter a median follow-up of 53.7 months, 77 patients were alive and 12 had died, of which 4 following metastatic progression. The 5-year and 8-year survival rates (CI95%) are, respectively, 90.2% (78.9-95.6%) and 69.8% (46.4-84.4%). The 5-year biochemical progression-free survival rate (CI95%) is 50.8% (36.7-63.3). Metastatic recurrence occurred in 11.2% of the patients. We did not find any statistically significant impact from the various known prognostic factors for biochemical progression-free survival. No toxicity with a grade of > or = to 3 was found.ConclusionsOur series is one of the largest published to date. Salvage radiotherapy has its place in the management of patients with biochemical progression with local recurrence in the prostate bed, with an acceptable toxicity profile. The interest of the boost is to be evaluated in prospective trials.

Neoadjuvant Chemotherapy and Concomitant Boost Radiotherapy in the Treatment of Locally Advanced Rectal Cancer

Aims: This study aimed to examine the efficacy and toxicities of concomitant boost three-dimensional conformal radiotherapy along with multidrug chemotherapy (capecitabine and oxaliplatin) in neoadjuvant course for locally advanced rectal cancer (LARC). Study Design: A phase II interventional nonrandomized study. Place and Duration of Study: This Study was conducted at Clinical Oncology and nuclear medicine department of Mansoura University Hospitals (Egypt) between November 2016 and October 2019. Methodology: Thirty patients (18 women, 12 men; age range 18-75 years) with (cT3-T4 and/or cN+) histologically confirmed rectal adenocarcinoma located within 12 cm of the anal verge were included in this study. Patients received three-dimensional conformal radiotherapy (3DCRT) to the pelvis of 45 Gy and a concomitant boost of 10 Gy to the primary tumor in 25 fractions, and concurrent with oxaliplatin (50 mg/m2 d1 weekly) and capecitabine (625 mg/m2 bid d1–5 weekly). Radical surgery was scheduled six to eight weeks after chemoradiation. Acute toxicities were recorded according to Common Terminology Criteria for Adverse Event (CTCAE) v5.0. Potential prognostic factors were evaluated using a binomial logistic regression. Survival curves were estimated using the Kaplan-Meier method and compared with Log-rank test. Results: All patients received chemoradiation. Twenty-seven patients underwent surgical resection. Twenty-five patients underwent sphincter-sparing surgery (92.6%) and nine patients (33.3%) achieved pathological complete response (pCR). The incidences of grade III neutropenia, diarrhea, and radiation dermatitis were 6.7%, 6.7%, 3.3% respectively. The three-year local recurrence (LR), disease-free survival (DFS) and overall survival (OS) rates were 7.4%, 63% and 74.1%, respectively. We found pre-surgical negative nodal status to be significantly associated with pCR (p=0.009). The pathological nodal stage was an independent prognostic factor to DFS. Conclusion: The combination of oxaliplatin, capecitabine, and dose escalation using concomitant boost 3DCRT is safely administrated in patients with locally advanced rectal adenocarcinoma and it offers high pCR and sphincter preservation rate.

TO COMPARE THE EFFICACY OF CONCOMITANT BOOST RADIOTHERAPY AGAINST CONCURRENT CHEMORADIATION IN LOCALLY ADVANCED HEAD AND NECK CANCER (OROPHARYNX/LARYNX/ HYPOPHARYNX)

Background: Most head and neck cancers, indeed 95% or more, are squamous cell carcinomas (SCC) and variants thereof, originating from the epithelium of the mucosal lining of the upper aerodigestive tract (UADT), and adenocarcinomas from associated secretory glands. Methods: This prospective randomized study was conducted in the Department of Radiation Therapy & Oncology, Regional Cancer Centre, IGMC, Shimla and patients were enrolled for a period of one year, from July 2012 to July 2013.It included all the eligible, previously untreated patients of squamous cell carcinoma of Head and Neck with histologically confirmed diagnosis and no evidence of distant metastasis. The sites included were oro-pharynx, hypo-pharynx and larynx with stages III, IV A and IV B. Results: On first follow up, overall there was complete response at nodal site in 50 patients(69.4%) 26 in CRT arm (70.3%) and 24 in ART arm(68.6%), however the difference was not statistically significant (p=0.875). Conclusion: There was comparable locoregional disease control with the use of accelerated six fractions a week radiation therapy compared to concomitant chemoradiation with conventional fractionation. Keywords: Six fraction, Concomitant chemoradiation, Conventional fractionation.