Targeted Radiotherapy Using Contact X-ray Brachytherapy 50 kV.

Rectal adenocarcinoma is a quite radioresistant tumor. In order to achieve non-operative management (NOM) radiotherapy plays a major role. Targeted radiotherapy aiming at high precision 3D radiotherapy uses stereotactic image-guided external beam radiotherapy machines. To further safely increase the tumor dose, endocavitary brachytherapy (ECB) is an original approach. There are two different ways to perform such an ECB: contact X-ray brachytherapy (CXB) using a 50 kV X-ray generator with an X-ray tube positioned under eye guidance into the rectal cavity and high-dose-rate brachytherapy (HDRB) using iridium-192 sources positioned into the rectal cavity under image guidance. This study focused on CXB. CXB uses a small mobile generator that produces 50 kV X-rays with limited penetration. This technique is well adapted to accessible tumors of limited size and especially needs a high dose rate (≥15 Gy/minutes) for rectal tumors. It is performed on an ambulatory basis. A total dose between 80−110 Gy is delivered in 3−4 fractions over 3 to 6 weeks into a small volume (5 cm3). CXB was pioneered in the 1970s by Papillon using the Philips RT 50TM. Since 2009, the Papillon P50TM has been used in 11 institutions in Europe. The OPERA Phase III trial tested the hypothesis that a CXB boost (90 Gy/3 fr) compared to an EBRT boost (9 Gy/5 fr) for T2−T3 ab < 5 cm and N0−N1 < 8 mm will increase the 3-year organ preservation (OP) rate when combined with 45 Gy/5 weeks with concomitant capecitabine. Out of more than 300 patients with tumors < 3 cm (1962−1992), Papillon reported a long-term local control close to 85%. Similar results were published in Europe and USA at that time. The Lyon R96-2 Phase III trial (2004) demonstrated that, when combined with preoperative EBRT, a CXB boost (90 Gy/3 fr) significantly increased the rate of clinical complete response (cCR) and sphincter preservation, with some patients having OP at 10 years. With more than 2000 patients treated in Europe (2010−2020) using the Papillon 50TM, organ preservation appears possible in close to 80% of cases in selected early T2−T3. The OPERA trial closed after 141 inclusions (2015−2020) after an independent data monitoring committee recommendation because of promising results. At the 2-year follow-up (blinded data), the rate of cCR and OP were 77% and 72%, respectively, for the 141 tumors, and for T < 3 cm (61 pts), they were 86% and 85%, respectively, with good bowel function. The final results should be available in 2022. Organ preservation using NOM appears to be a promising approach for rectal cancer. A CXB boost with chemoradiotherapy in selected early T2−T3 could become an attractive option to achieve a planned OP. This approach should be proposed to well-informed patients after discussion in an MDT.

Propensity score analysis of radical proctectomy versus organ preservation using contact X-ray brachytherapy for rectal cancer.

INTRODUCTION: Radical proctectomy (RP-TME) with neo adjuvant chemoradiotherapy (nCRT) remains the standard treatment for T2-T3 rectal cancer. Organ preservation (OP) using CRT and a "watch and wait" strategy (W&W) is a field of research. Planned organ preservation can be proposed for early T1-T3 using contact X-ray brachytherapy (CXB). We compared the oncological outcomes of both approaches using a propensity score matched-cohort analysis. MATERIAL AND METHODS: For comparative analyses between patients with nCRT + RP-TME and patients with CXB + CRT, propensity scores were calculated with logistic regression and multiple imputations for missing data. The variables included in the propensity score model were PS status, T-N stage and rectal circumference extension. Patients were matched 1:1 using the nearest neighbor method with a 0.1 caliper restriction. The 5-year Cancer Specific survival was the primary end point. RESULTS: The Accord 12 phase III trial included 584 patients who treated with nCRT + RP-TME. The CXB cohort included 71 patients with a planned OP. To select OP patient candidate, T4, tumor with extension >66% circumference were eliminated and only patients treated with CXB + CRT were analyzed in the CXB cohort resulting in a total of 374 patients. A one to one paired cohort with 36 patients in each group was derived. These two cohorts were well matched for all confounding factors except for age. The 5-year cancer specific rate showed no significant difference between the two groups (89% in Accord 12 vs 82% in CXB; p = 0.84). At 5 years, rate of metastasis (15% vs 22%, p = 0.54) showed no significant difference. In the CXB group 33/36 patients preserved their rectum. CONCLUSION: The organ preservation strategy using CXB boost yielded a 5-year cancer specific survival rate similar to patients treated with RP-TME. In selected early T2-3 rectal adenocarcinoma an organ preservation strategy could be offered as a reasonable option.

Brachytherapy for oligometastatic prostate cancer to the penis.

The origin of penile metastases is in 70% of cases from primary pelvic cancers (genitourinary and recto-sigmoid primary tumors). The prognosis is poor and it is often associated with synchronous bone metastases at the time of diagnosis. We present the case of a 61-year-old patient who developed a penile induration 7 years after radical prostatectomy followed by adjuvant external beam radiation therapy for high-risk prostatic adenocarcinoma. Biopsies confirmed the metastatic localization and a detailed assessment failed to find any further remote lesions. Faced with this penile oligometastatic prostate cancer, we proposed an ablative treatment based on interstitial multi-catheter high-dose rate brachytherapy. At the six-month follow-up, clinical examination and 68Ga-PSMA-11-PET confirmed a complete response of the penile tumor without new lesion at a distance.

APBI Versus Ultra-APBI in the Elderly With Low-Risk Breast Cancer: A Comparative Analysis of Oncological Outcome and Late Toxicity.

PURPOSE: Accelerated partial breast irradiation (APBI) represents a validated technique for low-risk breast cancer. Recently, ultra-APBI (uAPBI) using fewer than 5 fractions was described in the literature. We compared clinical outcomes and late toxicity after APBI or uAPBI in older patients. METHODS AND MATERIALS: Two cohorts of older patients (aged ≥70 years) with low-risk breast cancer treated with APBI (interstitial brachytherapy) were analyzed retrospectively. A total dose of 34 Gy in10 fractions (APBI) or 16 Gy in 1 fraction (uAPBI) was delivered from 2004 to 2012 and from 2013 to 2018, respectively. Oncologic outcome analyzed the cumulative incidence of local relapse, regional relapse, and distant metastases with disease-free survival, cause-specific survival, and overall survival. Late toxicity and cosmetic results were investigated. RESULTS: One hundred fifty-seven patients (APBI, n = 109 patients; uAPBI, n = 48 patients) underwent APBI according to the same selection criteria. Apart from the median follow-up (97 vs 72 months for APBI and uAPBI; P < .002), no significant difference was noted between the 2 groups. Regarding 6-year oncologic outcome, no significant difference was observed between APBI and uAPBI for local recurrence (1.3% vs 0%; P = .4), regional recurrence (2.5% vs 2.3%; P = .9), distant metastases (4.3% vs. 2.4%; P = .6), disease-free survival (85.2% vs. 82.2%; P = .8), cause-specific survival (96.7% vs. 96.2%; P = .9), and overall survival (86.7% vs. 82.2%; P = .7). Regarding late toxicity, no significant difference was observed between APBI and uAPBI (total complication number, 45 vs 33%; P = .173) with only grade 1 (88.4% vs. 95%) and grade 2 (11.6% vs. 5%) late toxicities (P = .677). Similarly, no significant difference was observed for excellent/good cosmetic results between the 2 cohorts (P = .98). CONCLUSIONS: We report the first study comparing APBI versus uAPBI in a cohort of older patients with low-risk breast cancer. No significant difference was found between the 2 treatment groups regarding oncologic outcome, late toxicity, and cosmetic result. uAPBI based on a single fraction of brachytherapy represents an attractive option for therapeutic de-escalation in older patients with breast cancer.

Clinical response assessment after contact X-Ray brachytherapy and chemoradiotherapy for organ preservation in rectal cancer T2-T3 M0: The time/dose factor influence.

INTRODUCTION: A neoadjuvant treatment aimed at rectal preservation should achieve a clinical complete response. This study comparing neoadjuvant treatment initiated with Contact X-ray (CXB) or External Beam radiotherapy (EBRT) is evaluating the influence of the time/dose parameter on clinical response during the first six months. MATERIALS AND METHODS: This retrospective consecutive series included T2-3 rectal adenocarcinoma staged using digital examination (DRE), endoscopy, magnetic radiation imaging and/or endorectal ultrasound. All patients were treated with organ preservation intent. Treatment protocol combined CXB (80-110 Gy/3-4 fractions) and EBRT ± concurrent capecitabine. In tumor exceeding 3.5 cm treatment was often initiated using EBRT. Clinical response was assessed (DRE, proctoscopy ± imaging) at very close interval between 2 weeks and 6 months after treatment initiation. RESULTS: Between 2002 and 2017, 61 patients (T2: 31; T3: 30) M0 (median age: 76 years) were treated. Treatment was initiated in 40 patients (T2: 28, T3: 12) with contact X-ray and in 21 (T2: 4, T3: 17) with EBRT. Using contact X-ray or EBRT first treatment, clinical complete (or near complete) response at week 14(±1) was respectively 88% [95CI:74-96] and 33% [95CI:15-57]. In multivariate analysis the treatment chronology was the most significant factor influencing cCR (OR: 7.53). At 6 months, with contact X-ray first all patients were in clinical complete response and five with EBRT remained in partial response. With 61 months median follow-up time, the local recurrence rate was 10% [95% CI: 6-16] at 5 years. T3 and fungating tumors were at higher risk of local recurrence. Organ preservation with good function was achieved in 95% of cases. CONCLUSION: This non randomized study tends to show that in early T2-3 tumors, a strategy using upfront contact therapy, which is reducing the overall treatment time, is an option allowing a more favorable outcome than EBRT first.

Second conservative treatment for second ipsilateral breast tumor event: A systematic review of the different re-irradiation techniques.

AIM: To address the different partial breast re-irradiation techniques available in the context of second conservative treatment (SCT), as an alternative to salvage mastectomy, for 2nd ipsilateral breast tumor event (IBTE) and summarize their respective oncological and toxicity outcomes. MATERIAL AND METHODS: A literature search was made based on MeSH/PubMed, including papers from 1995 to 2019. Each article was described according to the main irradiation technique, fractionation, oncological results and grade 3 toxicities related to the salvage conservative treatment. RESULTS: Twenty-two articles were identified, reporting the outcomes of over 1 000 patients. MIB Brachytherapy was the most used re-irradiation technique in case of SCT, with a median 3rdIBTE-FS rate of 88% and summed up grade 3 toxicities of 6%. As for IORT, the average rate of 3rdIBTE-FS was about Finally, external beam partial re-irradiation was recently tested in this indication with encouraging results in terms of tolerance. CONCLUSION: When presenting a 2ndIBTE, a SCT can safely be proposed to carefully selected and well-informed patients, as an alternative to salvage mastectomy. MIB appears to be the first intention and most robust choice. IORT, external beam radiotherapy and balloon brachytherapy are interesting alternatives but have only been tested in small series. Further investigations are required and their use should be limited to clinical trial only.

Mitomycin and 5-fluorouracil for second-line treatment of metastatic squamous cell carcinomas of the anal canal.

BACKGROUND: Metastatic squamous cell carcinomas (SCC) of the anal canal are rare and there is no international consensus on their second-line management. 5-Fluorouracil (5-FU) and mitomycin in combination with radiotherapy is the standard for locally advanced forms but its efficacy in metastatic stage has never been evaluated. PATIENTS AND METHODS: We report a retrospective analysis of patients treated with 5-FU and mitomycin from 2000 to 2017 in our institution for a metastatic SCC of the anal canal after failure of platinum-based regimen. The main outcome was progression-free survival (PFS) and the secondary outcomes were overall survival (OS), response rate, and toxicity. RESULTS: Nineteen patients, 15 women and four men, with a median age of 57 years were identified (range, 40-79 years). Patients received a median of three cycles (1-7) of mitomycin 5-FU. A dose reduction was necessary in six patients (31.6%), one patient had to discontinue treatment following toxicity and no death was due to treatment toxicity was reported. An objective response was observed in five patients (26.4%, 95% CI 6.6-46.2) including one complete response, six patients (31.6%, 95% CI 10.7-52.5) showed tumor stabilization. Median PFS and OS were 3 months [95% CI 1-5] and 7 months [95% CI 2.2-11.8]. Responder had a median duration of response of 4 months [95% CI 1.8-6.1] and one patient had 23 months duration of response. No significant difference was noted for PFS and OS for patients previously treated with mitomycin and 5-FU at a local stage. CONCLUSION: Mitomycin and 5-FU regimen provides tumor control with acceptable tolerance. It is an option for patients with metastatic SCC of the anal canal after failure of platinum-based chemotherapy. [Correction added on 9 October 2019, after first online publication: '5-FU' was inadvertently removed from the Results and Conclusion and has now been added to the text.].

GEC-ESTRO APBI classification as a decision-making tool for the management of 2nd ipsilateral breast tumor event.

AIM: Second ipsilateral breast tumor event (2ndIBTE) occurring after primary radio-surgical treatment can be treated by either salvage mastectomy or 2nd conservative treatment (2ndCT) including an accelerated partial breast re-irradiation (APBrI). We analyzed the impact of the GEC-ESTRO APBI classification (GAC) on the oncological outcome after APBrI. MATERIALS AND METHODS: Between 2000 and 2016, 159 patients (pts) underwent a 2ndCT. After lumpectomy, APBrI was performed using either low-dose (30-55 Gy reference isodose) or high-dose rate brachytherapy (28-34 Gy). Oncological outcome including 3rdIBTE, regional (RFS) or metastasis-free survival (MFS), specific (SS) and overall survival (OS) was analyzed according to GAC. Univariate (UVA) and multivariate analyses (MVA) were conducted to identify significant prognostic factors for 3rdIBTE. RESULTS: With a median follow-up of 71 months (range 62-85 months), 60 pts (42%), 61 pts (42.7%) and 22 pts (15.4%) were classified as low-risk (LR), intermediate-risk (IR) and high-risk (HR), respectively. For the whole cohort, 6-year 3rdIBTE-free survival, RFS, MFS, SS and OS rates were 97.4, 96.4, 90.3, 92.9 and 91.2%, respectively. Six-year 3rdIBTE-free survival rates for LR, IR and HR were 100, 95.8 and 92.9%, respectively (p = 0.003), while no significant differences were found between the three GAC groups for RFS, MFS, SS. In UVA, lympho-vascular invasion (p = 0.009), positive margins (p = 0.0001) and GAC high-risk group (p = 0.001) were considered as significant prognostic factors for 3rdIBTE, while, in MVA, high-risk group (p = 0.009) was the only prognostic factor. CONCLUSION: In case of 2ndIBTE, GAC could be used as a decision helping tool to discuss conservative or radical treatment options. Patient information remains crucial in order to accurately define the salvage therapy modalities.

Single fraction of accelerated partial breast irradiation in the elderly: early clinical outcome.

BACKGROUND: To analyze the clinical outcome of elderly women with early breast cancer who underwent accelerated partial breast irradiation (APBI) based on a post-operative single fraction of multicatheter interstitial high dose-rate brachytherapy (MIB). METHODS: A single institution retrospective cohort study was performed focusing on elderly patients (≥ 65 years old) presenting a low-risk breast carcinoma treated by lumpectomy plus axillary evaluation followed by MIB. A single fraction of 16 Gy was prescribed on the 100% isodose. Clinical outcome at 3 years was reported based on local relapse free survival (3-y LRFS), specific survival (SS) and overall survival (OS). Acute (< 180 days after APBI) and late toxicity were evaluated. Cosmetic results were clinically evaluated by the physician. RESULTS: Between January 2012 and August 2015, 48 women (51 lesions) were treated. Median age was 77.7 years (range: 65-92) with a median tumor size of 12 mm (range: 3-32). Five patients (pts) presented an axillary lymph node involvement (4 Nmic, 1 N1). Invasive ductal carcinoma was the most frequent histology type (86.3%). With a median follow-up of 40 months (range: 36-42), no local relapse occurred while 1 pt. developed axillary relapse (2.1%). The 3-y LRFS, SS and OS rates were 100%, 100% and 93.1% respectively. Forty-five acute events were remained. The most frequent acute toxicity was grade (G) 1 hyperpigmentation (26.7%), 3 pts. (6.3%) presented G3 acute toxicity (2 breast hematomas, 1 breast abscess). No ≥ G3 late toxicity was observed while 15 late toxicities occurred (G1: 13 events - 86.7%) mainly breast fibrosis). The rate of excellent cosmetic outcome was 76.4%. CONCLUSION: We reported promising and encouraging clinical outcome of a post-operative single fraction of MIB ABPI in the elderly. This approach leads to consider a sfAPBI as an attractive alternative to intra-operative radiation therapy while all the patients will be good candidates for APBI in regards to the post-operative pathological report. More mature results (number of patients and follow-up) are needed.