Dose-escalation in prostate cancer: Results of randomized trials.

In 1998, an editorial from the International Journal of Radiation Oncology - Biology - Physics (IJROBP) on the occasion of the publication of Phase I by Zelefsky et al. on 3D radiotherapy dose escalation asked the question: "will more prove better?". More than 20 years later, several prospective studies have supported the authors' conclusions, making dose escalation a new standard in prostate cancer. The data from prospective randomized studies were ultimately disappointing in that they failed to show an overall survival benefit from dose escalation. However, there is a clear and consistent benefit in biochemical recurrence-free survival, which must be weighed on an individual patient basis against the potential additional toxicity of dose escalation. Techniques and concepts have become more and more precise, such as intensity modulated irradiation, simultaneous integrated boost, hypofractionated dose-escalation, pelvic irradiation with involved node boost or focal dose-escalation on gross recurrence after prostatectomy. The objective here was to summarize the prospective data on dose escalation in prostate cancer and in particular on recent advances in the field. In 2022, can we finally say that more has proven better?

[The role of proton therapy in esophageal cancer]. / Le rôle de la protonthérapie dans les cancers de l'oesophage.

Because of the physical properties of proton beam radiation therapy (PT), which allows energy to be deposited at a specific depth with a rapid energy fall-off beyond that depth, PT has several theoretical advantages over photon radiation therapy for esophageal cancer (EC). Protons have the potential to reduce the dose to healthy tissue and to more safely allow treatment of tumors near critical organs, dose escalation, trimodal treatment, and re-irradiation. In recent years, larger multicenter retrospective studies have been published showing excellent survival rates, lower than expected toxicities and even better outcomes with PT than with photon radiotherapy even using IMRT or VMAT techniques. Although PT was associated with reduced toxicities, postoperative complications, and hospital stays compared to photon radiation therapy, these studies all had inherent biases in relation with patient selection for PT. These observations were recently confirmed by a randomized phase II study in locally advanced EC that showed significantly reduced toxicities with protons compared with IMRT. Currently, two randomized phase III trials (NRG-GI006 in the US and PROTECT in Europe) are being conducted to confirm whether protons could become the standard of care in locally advanced and resectable esophageal cancers.

HPV ctDNA detection of high-risk HPV types during chemoradiotherapy for locally advanced cervical cancer.

BACKGROUND: Chemoradiotherapy (CRT) is the standard of care for patients diagnosed with locally advanced cervical cancer (LACC), a human papillomavirus (HPV)-related cancer that relapses in 30%-60% of patients. This study aimed to (i) design HPV droplet digital PCR (ddPCR) assays for blood detection (including rare genotypes) and (ii) monitor blood HPV circulating tumor DNA (HPV ctDNA) levels during CRT in patients with LACC. METHODS: We analyzed blood and tumor samples from 55 patients with HPV-positive LACC treated by CRT in a retrospective cohort (n = 41) and a prospective cohort (n = 14). HPV-ctDNA detection was carried out by genotype-specific ddPCR. RESULTS: HPV ctDNA was successfully detected in 69% of patients (n = 38/55) before CRT for LACC, including nine patients with a rare genotype. HPV-ctDNA level was correlated with HPV copy number in the tumor (r = 0.41, P < 0.001). HPV-ctDNA positivity for HPV18 (20%, n = 2/10) was significantly lower than for HPV16 (77%, n = 27/35) or other types (90%, n = 9/10, P = 0.002). HPV-ctDNA detection (positive versus negative) before CRT was associated with tumor stage (P = 0.037) and lymph node status (P = 0.02). Taking into account all samples from the end of CRT and during follow-up in the prospective cohort, positive HPV-ctDNA detection was associated with lower disease-free survival (DFS) (P = 0.048) and overall survival (OS) (P = 0.0013). CONCLUSION: This is one of the largest studies to report HPV-ctDNA detection before CRT and showed clearance of HPV ctDNA at the end of treatment in most patients. Residual HPV ctDNA at the end of CRT or during follow-up could help to identify patients more likely to experience subsequent relapse.

[Moderate or extreme hypofractionation and localized prostate cancer: The times are changing]. / Hypofractionnement modéré ou extrême et cancers prostatiques localisés : les temps sont en train de changer.

There are many treatment options for localized prostate cancers, including active surveillance, brachytherapy, external beam radiotherapy, and radical prostatectomy. Quality of life remains a primary objective in the absence of superiority of one strategy over another in terms of specific survival with similar long-term biochemical control rates. Despite a significant decrease in digestive and urinary toxicities thanks to IMRT and IGRT, external radiotherapy remains a treatment that lasts approximately 2 months or 1.5 months, when combined with a brachytherapy boost. Given the specific radiosensitivity of this tumor, several randomized studies have shown that a hypofractionated scheme is not inferior in terms of biochemical control and toxicities, allowing to divide the number of fractions by a factor 2 to 8. Given that SBRT becomes a validated therapeutic option for a selected population of patients with localized prostate cancer, extreme hypofractionation is becoming a strong challenger of conventional external radiotherapy or brachytherapy.

Survival after breast cancer local recurrence according to therapeutic strategies.

AIMS: To compare survival outcomes after mastectomy (Mt) and lumpectomy plus interstitial brachytherapy (LpIB) in the treatment of breast cancer local recurrence (LR) occurring after conservative surgery. METHODS: Medical records of patients treated for an isolated LR from January 1, 1981 to December 31, 2009 were reviewed. To overcome the bias due to the fact that treatment choice (Mt or LpIB) was based on prognostic factors with LpIB proposed preferentially to women with good prognosis, Mt and LpIB populations were matched and compared with regard to overall survival (OS) and metastasis free survival (MFS). RESULTS: Among 348 patients analyzed, 66.7% underwent Mt, 17.8% LpIB and 15.5% Lp alone. After a median follow-up of 73.3 months, 65 patients had died (42/232 Mt, 8/62 LpIB, 15/54 Lp). Before matching, OS and MFS at 5 years were significantly better in the LpIB compared to the Mt group, due to significantly more frequent poor prognostic factors in the latter (p = 0,07 and p = 0,09 respectively, log-rank significance limit of 10%). After matching, the benefits of LpIB disappeared since MFS and OS rates were not significantly different in both groups (p = 0.68 and 0.88 respectively). After LpIB, the second LR rate was 17% at 5 years and 30% at 10 years. CONCLUSION: A second conservative breast cancer treatment associating lumpectomy and interstitial brachytherapy is possible for selected patients with LR, without decrease in neither OS nor MFS compared to mastectomy.

Early stage cervical cancer: Brachytherapy followed by type a hysterectomy versus type B radical hysterectomy alone, a retrospective evaluation.

BACKGROUND: Two options are possible for the management of early stage cervical cancer, without lymph node involvement: radical surgery or brachytherapy followed by surgery. The aim of this study was to compare overall survival (OS) and disease-free survival (DFS) of early stage cervical cancers managed by uterovaginale brachytherapy followed by extrafasciale hysterectomy (group 1) or by radical hysterectomy alone (group 2). The secondary objectives were to compare the morbidity of these two different approaches and to evaluate the parametrial involvement rate in patients managed by radical hysterectomy. MATERIALS AND METHODS: It is a retrospective and collaborative study between the Paoli Calmettes Institute (Marseille) and the Oscar Lambret Center (Lille) from 2001 to 2013, in patients with tumors FIGO stages IA1, IA2, IB1 and IIA less than 2 cm of diameter, without pelvic lymph node involvement. RESULTS: One hundred and fifty-one patients were included (74 in group 1 and 77 in group 2). The demographic characteristics of the two groups were comparable. OS and DFS were respectively 92.3% versus 100% (p = 0.046) and 92.3% and 98.7% (p = 0.18). Complication rates were 12.2% and 44.2%, respectively (p < 0.0001). In group 2, the parametrial invasion rate in this study was 1.30%. CONCLUSION: In our study, the two strategies are comparable in terms of DFS. Complications seem more frequent in the group 2, but more severe in the group 1. Finally, the low rate of parametrial invasion in group 2 confirms the interest of a less radical surgical treatment in these stages with good prognosis.

Calcifications and tungsten deposits after breast-conserving surgery and intraoperative radiotherapy for breast cancer.

AIM: To describe the presence of atypical calcifications on post-operative mammography after breast-conserving surgery (BCS) and intraoperative radiotherapy (IORT). MATERIALS AND METHODS: We retrospectively include all patients followed after BCS and IORT for breast cancer (n=271). All follow-up mammograms at 6 months after surgery were retrospectively evaluated by two board-certified radiologists. The radiologists had to notify the presence or the absence of atypical calcifications. RESULTS: Five patients had on follow-up mammography the presence of atypical calcifications. Two patients had a stereotactic breast biopsy. The pathologic examination showed the presence of small tungsten particles located in the breast parenchyma. CONCLUSION: The presence of atypical calcifications after BCS and IORT, presenting as multiple, scattered, round calcifications, should be rated as BIRADS 2 and do not require biopsy. They corresponded on tungsten deposits.

[Adenoid cystic carcinoma of the head and neck: a retrospective series of 169 cases]. / Carcinomes adénoïdes kystiques ORL : étude rétrospective multicentrique de 169 cas.

PURPOSE: Adenoid cystic carcinoma represents 1% of head and neck cancers. Adenoid cystic carcinomas are slow growing tumours with high potential for local recurrence. Treatment usually associates radiotherapy and surgery, but the role of radiotherapy remains unclear. We report a retrospective multicentric study of the management and prognostic factors of 169 adenoid cystic carcinomas of head and neck. PATIENTS AND METHODS: Between 1982 and 2010, 169 patients with adenoid cystic carcinoma of the head and neck were referred to the Cercle des oncologues radiothérapeutes du Sud departments of radiotherapy either for primary untreated tumour (n=135) or for a recurrence of previously treated tumour (n=34). The site of adenoid cystic carcinoma was: parotid gland (n=48, 28.4%), minor salivary gland (n=35, 20.7%), submandibular gland (n=22, 13%), sinus cavities (n=22, 13%), other (n=42, 24.9%). Tumour stages were: T1 (12.4%); T2 (14.2%); T3 (12.4%); T4 (41.4%) and Tx (19.5%). Lymph node involvement was 13% and distant metastasis 8.9%. For adenoid cystic carcinomas of the parotid gland, major nerve involvement was evaluated. Preferential site of metastasis was the lung (87.5%). Treatments were: surgery alone (n=27), surgery and adjuvant radiotherapy (n=89), surgery and adjuvant chemoradiotherapy (n=12), exclusive chemoradiotherapy (n=13), exclusive radiotherapy (n=14), other associations (n=5) and no treatment (n=7). Radiotherapy was delivered through photons (n=119), neutrons (n=6), both (n=4). Two patients had a brachytherapy boost. Median prescribed doses to T and N were respectively 65 Gy and 50 Gy for the 119 photons treated patients. RESULTS: Mean follow-up was 58 months (range 1-250 months). As of December 1, 2010, 83 patients were alive with no evolutive disease (49%), 35 alive and had recurred, 18 had uncontrolled evolutive disease, 28 had died of adenoid cystic carcinoma and 5 of intercurrent disease. Overall survival and disease free survival were respectively 72% and 72% at 5 years, 53% and 32% at 10 years; 5 and 10-year freedom from local recurrence were 81% and 52% respectively. Nerve involvement was found in 17/48 parotid gland adenoid cystic carcinomas. The Cox model including all patients, showed that surgery (P<0.001), surgical margins (P=0.015), nerve involvement (P=0.0079), length of radiotherapy (P=0.018), and tumour location (P=0.041) were associated with disease free survival. CONCLUSION: In this large series of adenoid cystic carcinoma of head and neck with a majority of T3-T4 tumours, 10-year survivals were achieved for 50% of patients. Radiotherapy did not impact survival.

Is neoadjuvant chemotherapy prior to radio-chemotherapy beneficial in T4 anal carcinoma?

BACKGROUND: This study retrospectively describes the outcome of a series of 38 patients (pts) with T4 anal carcinoma exclusively treated by radio and chemotherapy. PATIENTS AND METHODS: From 1992 to 2007, 38 pts with UST4-N0-2-M0 anal carcinoma were treated with exclusive radiotherapy and chemotherapy. All patients received external beam radiotherapy (EBRT) (median dose 45 Gy) with a concomitant chemotherapy (5-fluorouracil-cisplatin). Eleven patients received neo-adjuvant chemotherapy (5-fluorouracil-cisplatin). After 2-8 weeks, a 15-20 Gy boost was delivered either with EBRT (20 pts) or interstitial (192)Ir brachytherapy (18 pts). Mean follow-up was 66 months. RESULTS: After chemoradiation therapy (CRT), 13 pts (34%) had a complete response, 23 pts (60%) a response >50% (2 pts were not evaluated). The 5-year-disease-free survival was 79.2 ± 6.5%, and the 5-year overall survival was 83.9 ± 6%. Eight patients developed tumor progression (mean delay 8.8 months), six of them requiring a salvage surgery with definitive colostomy for local relapse. Late severe complication requiring colostomy was observed in 2 pts. The 5-year-colostomy-free survival was 78 ± 6.9%. Patients who received primary chemotherapy had a statistically significant better 5-year colostomy-free survival (100% vs. 38 ± 16.4%, P = 0.0006). CONCLUSION: T4 anal carcinoma can be treated with a curative intent using a sphincter-sparing approach of CRT, and neo-adjuvant chemotherapy should be considered prior to radiotherapy.

[Radiation therapy of benign diseases. What's new eight years after?]. / La radiothérapie des affections bénignes: quelles indications huit ans plus tard?

The authors present an update version of the indications for radiotherapy in the management of benign diseases. This is based on available randomized trials and recent international meetings. Validated indications remain the prevention of resected heterotopic bone ossifications, keloïds scars and pterygium and also treatment of arteriovenous malformations; the place of radiotherapy for malignant exophtalmia is more and more restricted. Randomized trials have demonstrated the efficacy of endobrachytherapy in the prevention of restenosis after angioplasty but the use of embedded stent has replaced this indication. Macular degeneration is no more an indication of radiotherapy. Quality requirements for radiotherapy are identical for benign or malignant indications.

[The patient care experience in radiotherapy: perspectives for better patient support]. / Les enjeux du vécu de la radiothérapie: perspectives pour un meilleur accompagnement des malades.

This paper reports the patient care experience during the course of the radiotherapy. Plights are multiple. Patients are confronted with a complex and unknown distressing space, an irrelavant information, a banalization of side effects, an isolation with a frequent inadequate support of their family or the caregivers team, with the fear of a definitive abandonment at the end of the treatment without comforting follow-up. It is imperative to state a real policy in order to improve the patient support. Sensibilization and training of the caregivers, in spite of a frequent overbooking technical work, is required in a pluridisciplinary approach to provide a relevant reception with the collaboration of psychologists, social workers and self care groups and associations. The personal implication of the physicians and technologists is also essential. The simple smile is the intangible proof of the reliable emotional support.