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To report long-term oncological and toxicity outcomes after high-dose-rate brachytherapy (HDB) followed by oncologic surgery for patients with early-stage cervical cancer.From 2005 to 2019, all patients treated with preoperative HDB at Antoine Lacassagne Cancer Center for early-stage (IB1-IB2-IIA - FIGO 2018) cervical cancer with local relapse risk factors were included. HDB was performed followed by hysterectomy. Oncological and toxicity outcomes were evaluated prospectively.We identified 61 patients, with a median follow-up of 84 months. Posthysterectomy complete pathological response was observed in 46 patients (75.4%). Six patients (9.8%) experienced recurrence, including 4 local relapses (6.6%), and 2 deaths (3.3%) due to cervical cancer. Five-year local, nodal and metastatic relapse-free survivals were 94% (95% CI 87-100%), 96% (95% CI 90-100%) and 93% (95% CI 86-100%) respectively. Five-year overall survival was 98% (95% CI 95-100%). No grade ≥ 3 acute toxicity was observed, and 3 patients (4.9%) experienced grade 2 acute toxicity. One patient presented grade 4 late digestive toxicity, and 6 patients had grade 2 late toxicity. Only 1 patient still had grade 2 toxicity, after 9 years follow-up.To our knowledge, we are reporting the longest follow-up of a preoperative HDB cohort. With similar oncological outcomes and less morbidity compared to primary surgery treatment followed more or less by adjuvant radiotherapy, HDB followed by hysterectomy could be a promising therapeutic option for early-stage cervical cancers with poor prognostic factors.

Highlights • Key objective: the goal provides data to evaluate the oncological risk of performing a planned- conservative strategy in selected patients presenting early T2-T3 rectal adenocarcinoma. • Knowledge generated: This propensity score analysis on 72 patients, comparing neoadjuvant chemoradiotherapy followed by radical surgery with planned organ preservation using combined chemoradiotherapy and contact X-ray brachytherapy boost, showed no detrimental oncological safety results after 5 year follow-up. • Relevance: This study supplies additional arguments in favor of organ preservation for selected early rectal T2-T3., 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.

Highlights • Brachytherapy boost is a standard of care for locally advanced cervical cancer. • High-dose-rate brachytherapy (HDR-BT) boost procedure is not standardized. • The number of implants, fractions, doses and imaging differ in literature. • Bi-fractionated HDR-BT in 1 implant is feasible with good oncological outcome. • Bi-fractionated HDR-BT dose escalation slightly increases acute toxicity., Purpose Brachytherapy (BT) boost after radio-chemotherapy (RCT) is a standard of care in the management of locally advanced cervical cancer (LACC). As there is no consensus on high-dose-rate (HDR) BT fractionation schemes, our aim was to report the oncological outcome and toxicity profile of four different schemes using twice-a-day (BID) HDR-BT. Patients and methods This was an observational, retrospective, single institution study for patients with LACC receiving a HDR-BT boost. The latter was performed with a single implant and single imaging done on day 1. The different fractionation schemes were: 7 Gy + 4x3.5 Gy (group 1); 7 Gy + 4x4.5 Gy (group 2); 3x7Gy (group 3) and 3x8Gy (group 4). Local (LFS), nodal (NFS) and metastatic (MFS) recurrence-free survival as well as progression-free survival (PFS) and overall survival (OS) were analyzed. Acute (≤6 months) and late toxicities (>6 months) were reported. Results From 2007 to 2018, 191 patients were included. Median follow-up was 57 months [45–132] and median EQD210D90CTVHR was 84, 82 and 90 Gy for groups 2, 3 and 4 respectively (dosimetric data missing for group 1). The 5-year LFS, NFS, MFS, PFS and OS were 85% [81–90], 83% [79–86], 70% [67–73], 61% [57–64] and 75% [69–78] respectively, with no significant difference between the groups. EQD210D90CTVHR

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.

Resume Le cancer de la prostate oligometastatique est parmi les cancers oligometastatiques les plus etudies dans la litterature. Malgre cela, a ce jour, nous disposons de peu d’etudes prospectives ayant evalue la radiotherapie stereotaxique des oligometastases du cancer de la prostate. Deux essais randomises de phase II montrent un benefice en termes de survie sans progression en comparaison avec une surveillance simple. Les donnees de registres prospectifs montrent egalement un tres bon taux de controle local et une faible toxicite. L’inclusion dans les essais en cours doit etre fortement encouragee afin de preciser la place de cette irradiation stereotaxique en complement du traitement systemique. La radiotherapie de la tumeur primitive a fait l’objet d’essais randomises, elle apporte un benefice de survie globale chez les patients atteints d’un faible volume tumoral. Le benefice est inversement correle au nombre de lesions osseuses sur l’imagerie classique, jusqu’a trois lesions. La radiotherapie de la tumeur primitive est recommandee par les societes savantes chez les patients atteints d’un faible volume tumoral. Sa place en association avec les hormonotherapies de nouvelle generation doit etre precisee.

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.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.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).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.

Purpose Breast cancer in the elderly has become a public health concern; there is a need to re-design its treatment with a view to de-escalation. Our paper sets out the rationale for a phase 3 randomized trial to evaluate less burdensome adjuvant procedures that remain effective and efficient. Materials and methods For low-risk breast cancer in the elderly, adjuvant treatment has been adjusted in order to make it more suitable and efficient. Hypofractionated radiation therapy based on accelerated or non-accelerated regimens as well as accelerated and ultra-accelerated partial breast irradiation (APBI) protocols were reviewed. Withdrawal of radiation (RT) or endocrine therapies (ET) from the adjuvant procedure were also investigated. Based on molecular and APBI classifications, inclusion criteria were discussed. Results Phase 3 randomized trials which compared standard vs. accelerated/non-accelerated hypofractionated regimens confirmed that the latter were non-inferior in terms of local control. Similarly, except for intraoperative-based techniques, APBI achieved non-inferior local control rates compared to whole breast irradiation for low-risk breast cancer. In phase 2 prospective trials using ultra APBI, encouraging results were observed regarding oncological outcome and toxicity profile. In phase 3 trials, adjuvant ET without RT significantly increased the rate of local relapse with no impact on overall survival while RT alone proved effective. Elderly patients aged 60 or more with low-risk, luminal A breast cancer were chosen as the target population in a phase 3 randomized trial comparing APBI + 5-year ET vs. uAPBI (16 Gy 1f) alone. Conclusion To investigate de-escalation adjuvant treatment for elderly breast cancer patients, we have defined a road map for testing more convenient strategies. This EPOPE phase 3 randomized trial is supported by the GEC-ESTRO breast cancer working group.

Purpose Second conservative treatment has emerged as an option for patients with a second ipsilateral breast tumor event after conserving surgery and breast irradiation. We aimed to address the lack of evidence regarding second breast event treatment by comparing oncologic outcomes after conservative treatment or mastectomy. Methods and Materials Oncologic outcomes were analyzed using a propensity score-matched cohort analysis study on patients who received a diagnosis of a second breast event between January 1995 and June 2017. Patient data were collected from 15 hospitals/cancer centers in 7 European countries. Patients were offered mastectomy or lumpectomy plus brachytherapy. Propensity scores were calculated with logistic regression and multiple imputations. Matching (1:1) was achieved using the nearest neighbor method, including 10 clinical/pathologic data related to the second breast event. The primary endpoint was 5-year overall survival from the salvage surgery date. Secondary endpoints were 5-year cumulative incidence of third breast event, regional relapse and distant metastasis, and disease-free and specific survival. Complications and 5-year incidence of mastectomy were investigated in the conservative treatment cohort. Results Among the 1327 analyzed patients (mastectomy, 945; conservative treatment, 382), 754 were matched by propensity score (mastectomy, 377; conservative treatment, 377). The median follow-up was 75.4 months (95% confidence interval [CI], 65.4-83.3) and 73.8 months (95% CI, 67.5-80.8) for mastectomy and conservative treatment, respectively (P = .9). In the matched analyses, no differences in 5-year overall survival and cumulative incidence of third breast event were noted between mastectomy and conservative treatment (88% [95% CI, 83.0-90.8] vs 87% [95% CI, 82.1-90.2], P = .6 and 2.3% [95% CI, 0.7-3.9] vs 2.8% [95% CI, 0.8-4.7], P = .4, respectively). Similarly, no differences were observed for all secondary endpoints. Five-year cumulative incidence of mastectomy was 3.1% (95% CI, 1.0-5.1). Conclusions To our knowledge, this is the largest matched analysis of mastectomy and conservative treatment combining lumpectomy with brachytherapy for second breast events. Compared with mastectomy, conservative treatment does not appear to be associated with any differences in terms of oncologic outcome. Consequently, conservative treatment could be considered a viable option for salvage treatment.

Introduction: To evaluate long term clinical outcome and prognostic factors after accelerated partial breast irradiation (APBI) in the elderly using high-dose-rate interstitial multi-catheter brachytherapy (HIBT).Material and methods: Between 2005 and 2018, 109 patients underwent APBI using HIBT (34 Gy/10f/5d or 32 Gy/8f/4d). Based on a prospective database, outcomes were retrospectively analyzed (local relapse-free survival (LRFS), metastatic-free survival (MFS), specific survival (SS) and overall survival (OS). Prognostic factors were investigated. Late toxicity and cosmetic evaluation were reported.Results: With a median follow-up of 97 months [7–159], median age was 81.7 years [58-89]. According to the GEC-ESTRO APBI classification, 72.5%, 11.9% and 15.6% were classified as low, intermediate and high-risk respectively. The histological type was mainly invasive ductal carcinoma (87.1%). The median tumor size was 10 mm [range 1-35]. Eight-year LRFS, SS and OS were 96.7% [95% CI [0.923; 1]), 96.7% [95% CI [0.924; 1] and 72%[95% CI [0.616; 0.837] respectively. In univariate analysis, APBI classification was not cosidered as prognostic factor, whilemolecular classification was prognostic factor for OS (pConclusion: Long-term follow-up confirms that HIBT is safe and effective for elderly early breast cancer. Our results suggest that selected elderly women presenting with high-risk breast cancer could be also considered for APBI.

Brachytherapy is part of the treatment of locally advanced cervical cancers, accounting for about half of the total delivered dose. The benefit of dose escalation is the most important in advanced cases or if the tumor has responded poorly. The use of interstitial implantations makes it possible to reach doses of the order of 85 to 90Gy (including external beam radiotherapy contribution) in most patients, through image-guided approaches. Brachytherapy delivery is one of the quality criteria for patient care. To date, no data allow us to consider as an alternative the use of external boost through intensity-modulated or stereotactic body radiotherapy. Indeed, the doses delivered to the tumor and the capacity to spare normal tissues remains lower, as compared to what is permitted by brachytherapy. It is therefore appropriate for centers that do not have access to the technique to establish networks with centers where brachytherapy is performed, to allow each patient to have access to the technique. It is also necessary to promote brachytherapy teaching. The issue of reimbursement will be crucial in the coming years to maintain expertise that is today insufficiently valued in its financial aspects, but has a very high added value for patients.

Highlights • Treatment initiation of T2-T3 rectal cancers with Contact (CXB) provides a fast clinical complete response. • In T2N0< 3 cm tumors, CXB first with chemoradiotherapy can achieve local control in more than 85%. • The Phase III OPERA trial should bring robust data in favor of CXB as initial treatment of T2N0< 3 cm., 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.

In recent years, results with mature follow-up have been reported for several Phase III trials randomizing women to receive whole breast irradiation (WBI) versus varying modalities of partial breast irradiation (PBI). It is important to recognize that these methods vary in terms of volume of breast tissue treated, dose per fraction, and duration of therapy. As such, clinical and technical guidelines may vary among the various PBI techniques.Members of the American Brachytherapy Society with expertise in PBI performed an extensive literature review focusing on the highest quality data available for the numerous PBI options offered in the modern era. Data were evaluated for strength of evidence and published outcomes were assessed.The majority of women enrolled on randomized trials of WBI versus PBI have been age45 years with tumor size3 cm, negative margins, and negative lymph nodes. The panel also concluded that PBI can be offered to selected women with estrogen receptor negative and/or Her2 amplified breast cancer, as well as ductal carcinoma in situ, and should generally be avoided in women with extensive lymphovascular space invasion.This updated guideline summarizes published clinical trials of PBI methods. The panel also highlights the role of PBI for women facing special circumstances, such as history of cosmetic breast augmentation or prior breast irradiation, and discusses promising novel modalities that are currently under study, such as ultrashort and preoperative PBI. Updated consensus guidelines are also provided to inform patient selection for PBI and to characterize the strength of evidence to support varying PBI modalities.

Among over 100 proton therapy centres worldwide in operation or under construction, French proton therapy is coming to full maturity with the recent opening of the Nice (1991, upgrade in 2016) and Caen (2018) facilities next to the Orsay (1991, upgrade in 2010) centre. Proton therapy is a national priority for children and young adults in all three centres. The patient-related activity of the three French centres is coordinated via the Protonshare portal to optimise referral by type of indication and available expertise in coordination with the French society of radiation oncology SFRO and French radiotherapy centres. The centres are recognised by the French Health Care excellence initiative, promoted by the ministry of Foreign Affairs. The three centres collaborate structurally in terms of clinical research and are engaged at the international level in the participation to European databases and research initiatives. Concerted actions are now also promoted in preclinical research via the Radiotransnet network. Ongoing French developments in proton therapy are well presented in international hadron therapy meetings, including European Proton Therapy Network and Particle Therapy Cooperative Oncology Group. Proton therapy teaching in France is offered at several levels and is open to colleagues from all radiation oncology centres, so that they are fully informed, involved and trained to facility recognition of possible indications and thereby to contribute to appropriate patient referral. This close collaboration between all actors in French radiation oncology facilitates the work to demonstrate the required level of medical and scientific evidence for current and emerging indications for particle therapy. Based on that, the future might entail a possible creation of more proton therapy facilities in France.

Standard adjuvant therapies for breast cancer such as chemotherapy or aromatase inhibitor and LH-RH agonist hormone therapy are associated with significant survival gains but also induce bone loss by aggravating the estrogen deprivation. The bone loss may be substantial, notably during early treatment, and occurs regardless of the baseline bone mineral density values. The objective of developing these recommendations was to achieve a practical consensus among various scientific societies, based on literature review, about osteoporosis prevention and treatment in these patients. The following scientific societies contributed to the work: Société Française de Rhumatologie (SFR), Groupe de Recherche et d'Information sur les Ostéoporoses (GRIO), Groupe Européen d'Etudes des Métastases Osseuses (GEMO), Association Francophone pour les Soins Oncologiques de Support (AFSOS), Société Française de Sénologie et de Pathologie Mammaire (SFSPM), Société Française de Radiothérapie Oncologique (SFRO). Drug prescription and reimbursement modalities in France were taken into account. These recommendations apply to postmenopausal women taking systemic chemotherapy and/or aromatase inhibitor therapy, non-postmenopausal women taking LH-RH agonist therapy, and non-postmenopausal women with persistent amenorrhea 1 year after chemotherapy completion. All women in these three categories should undergo an evaluation of bone health and receive interventions to combat risk factors for bone loss. Patients with a history of severe osteoporotic fracture and/or a T-score value-2.5 should receive osteoporosis drug therapy. The FRAX® score should be used to guide treatment decisions in patients whose T-score is between -1 and -2.5. General osteoporosis prevention measures should be applied in patients without criteria for osteoporosis drug therapy, who should undergo bone mineral density measurements 18-24 months later if the baseline T-score is-1 and 3-5 years later if the baseline T-score is-1. The anti-tumor effect of bisphosphonates and denosumab was not considered when establishing these recommendations.

Resume Les traitements adjuvants standards du cancer du sein comme la chimiotherapie et les hormonotherapies par inhibiteurs de l’aromatase et/ou analogues de la LH-RH sont associes a un gain significatif de survie des patientes mais sont responsables d’une perte osseuse parfois importante surtout en debut de traitement. Cette perte osseuse est due a la carence estrogenique supplementaire induite par ces traitements et s’observe quel que soit le niveau densitometrique initial des patientes. L’objectif de ces recommandations est de proposer, a la suite d’une revue de la litterature, une attitude consensuelle pratique pour la prevention et le traitement de l’osteoporose chez ces patientes, entre les differentes societes savantes qui ont participe a ce travail : Societe francaise de rhumatologie (SFR), Groupe de recherche et d’Information sur les osteoporoses (GRIO), Groupe europeen d’etudes des metastases osseuses (GEMO), Association francophone pour les soins oncologiques de Support (AFSOS), Societe francaise de senologie et de pathologie mammaire (SFSPM), Societe francaise de radiotherapie oncologique (SFRO), en tenant compte des modalites de prescription et de remboursement des traitements en France. Ces recommandations concernent les femmes menopausees recevant un traitement systemique par chimiotherapie et/ou inhibiteur d’aromatase, les femmes non menopausees recevant un agoniste de LH-RH et les femmes non-menopausees presentant une amenorrhee persistante 1 an apres l’arret de la chimiotherapie. Il est recommande que toutes ces femmes aient une evaluation osseuse et une prevention des facteurs de risque de perte osseuse. Il est recommande que les patientes aux antecedents de fracture osteoporotique severe et/ou ayant un T-score −1. Ces recommandations n’abordent pas l’action anti-tumorale des bisphosphonates ou du denosumab.

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. 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. 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. 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.

In order to provide more convenient irradiation regimens for patient comfort, radiation facility organization and health expenses, new hypofractionated protocols have been evaluated. Moderately (dose/fraction: 2.3 to 3Gy), then ultra (dose/fraction: 5.2 to 6.1Gy) hypofractionated irradiations were first validated. The current question is: is it possible to go forward using extreme hypofractionated regimens (EHR) based on 1 to 3 fractions. Different irradiation techniques are under investigation. However, brachytherapy remains the smartest way to deliver a high dose in a small volume. We report prospective and retrospective study results which evaluated EHR for breast and prostate brachytherapy. While oncological outcome and toxicity profile appear extremely encouraging for low-risk breast cancer after a 1 to 4 fractions (6.25 to 20Gy/fraction), the use of a single fraction of 19 to 23Gy appears debatable for prostate cancer. Brachytherapy represents an emblematic example of EHR but longer follow-up and more mature results are awaited in order to specify the right indications and refine the EQD2 calculation method including new biological and technical factors.

Purpose Evaluate efficacy and toxicity of hypofractionated stereotactic radiotherapy (HSRT) for patients treated for pituitary adenoma (PA) with an alternative HSRT escalating protocol delivering 35 Gy in 5 fractions. Material and methods From June 2007 to March 2017, 29 patients with pituitary adenoma were treated in Antoine Lacassagne Cancer Centre with an alternative HSRT protocol. Prescribed dose was 35 Gy in 5 fractions of 7 Gy. Radiographic responses were assessed by annual MRI. Hormone blood samples were evaluated each year after HSRT. Results A total of 29 patients aged between 23 and 86 years (median 54 years) were included. Twelve patients received HSRT for recurrent cases and 12 received postoperative adjuvant HSRT, 5 patients did not have surgery. After a median follow-up period of 47 months local control rate was 96%. One patient presented an out-field tumor regrowth 73 months after HSRT. The majority of PA were endocrine-active (18 patients, 62%). After HSRT, 8 patients (44%) presented complete response on initial secretion, 4 patients (23%) presented partial response on initial secretion. Four patients (14%) presented grade 2 or more acute radiation toxicities. One grade 4 visual disorder was observed for one patient. Conclusions HSRT delivering 35 Gy in 5 fractions represents a feasible treatment and shows promising results to reduce hormonal overproduction and to improve local control in PA.

The Papillon experience and the Lyon R96-02 trial have shown that contact X-ray brachytherapy of 50kV is efficient and safe to achieve long term local control and organ preservation for cT1 and early cT2-3 rectal cancers. The OPERA trial, using the Papillon 50™ machine, brings further support to this preservation strategy for selected T2T3ab lesions. Future trials using a contact X-ray boost will try to consolidate and enlarge its place in organ preservation for rectal cancers.

BackgroundThe conventional dose rate of radiation therapy is 0.01–0.05 Gy per second. According to preclinical studies, an increased dose rate may offer similar anti-tumoral effect while dramatically improving normal tissue protection. This study aims at evaluating the early toxicities for patients irradiated with high dose rate pulsed proton therapy (PT).Materials and MethodsA single institution retrospective chart review was performed for patients treated with high dose rate (10 Gy per second) pulsed proton therapy, from September 2016 to April 2020. This included both benign and malignant tumors with ≥3 months follow-up, evaluated for acute (≤2 months) and subacute (>2 months) toxicity after the completion of PT.ResultsThere were 127 patients identified, with a median follow up of 14.8 months (3–42.9 months). The median age was 55 years (1.6–89). The cohort most commonly consisted of benign disease (55.1%), cranial targets (95.1%), and were treated with surgery prior to PT (56.7%). There was a median total PT dose of 56 Gy (30–74 Gy), dose per fraction of 2 Gy (1–3 Gy), and CTV size of 47.6 ml (5.6–2,106.1 ml). Maximum acute grade ≥2 toxicity were observed in 49 (38.6%) patients, of which 8 (6.3%) experienced grade 3 toxicity. No acute grade 4 or 5 toxicity was observed. Maximum subacute grade 2, 3, and 4 toxicity were discovered in 25 (19.7%), 12 (9.4%), and 1 (0.8%) patient(s), respectively.ConclusionIn this cohort, utilizing high dose rate proton therapy (10 Gy per second) did not result in a major decrease in acute and subacute toxicity. Longer follow-up and comparative studies with conventional dose rate are required to evaluate whether this approach offers a toxicity benefit.

Resume La curietherapie, par son mode d’action, comme par ses resultats cliniques de haut niveau de preuve, represente une technique d’irradiation des cancers specifique dans la prise en charge des cancers comme de certaines rechutes en territoire irradie. Apres la periode faste des annees 1980–1990, la curietherapie a progressivement perdu de son attrait. Afin d’apporter une solution concrete a cette situation deletere, il est important que les tutelles, les organismes payeurs, les associations de patients, les specialistes d’organes et les oncologues radiotherapeutes comprennent les raisons qui ont conduit a une telle situation ainsi que les risques encourus. Un enseignement juge insuffisant, une valorisation inadaptee et une image vieillissante de la curietherapie constituent les trois raisons essentielles de cette degradation et representent les trois enjeux majeurs conditionnant son maintien dans l’arsenal therapeutique anticancereux. Une communication, adaptee au sein de la communaute des oncologues radiotherapeutes, comme avec les autres societes savantes, est primordiale de meme qu’aupres des tutelles et des associations de patients. Il est capital que la curietherapie soit (re)connue afin de lui rendre tout son interet pour les patients qui pourront en beneficier.

Highlights • Penile cancer is a rare tumor. • The organ preservation perspective makes the treatment challenging. • For early stage, conservative brachytherapy achieved excellent oncological outcome. • Conservative brachytherapy reported encouraging functional results. • HDR brachytherapy represents an attractive therapeutic option., Purpose To analyze the oncological outcome and toxicity profile after conservative treatment based on multicatheter interstitial high-dose rate brachytherapy (MHB) for patients presenting a localized penile cancer. Materials and methods Patients with histologically proven, non-metastatic (T1-T2 N0-N2 M0) localized penile cancer were treated with MHB. Needles were placed under general anesthesia into the target volume using a dedicated template. Treatment planning was performed using a post-implant CT-scan to deliver 35 Gy or 39 Gy (9f, 5d) for adjuvant or definitive treatment respectively. Five-year oncological outcome was evaluated with local relapse-free (LRFS), regional relapse-free (RRFS), and metastasis-free survival (MFS), specific (SS) and overall survival (OS). In pre-treatment and follow-up consultations, skin, urinary and sexual toxicities were investigated using CTCAEv4.0 classification, International Prostate Symptom Score (IPSS) and International Index of Erectile Function 5-items (IIEF-5). Dosimetry data were also analyzed. Results From 03/2006 to 05/2020, with a median follow-up of 72.4 months [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], 29 pts, mainly T1 (75.9%) and N0 (89.7%), underwent MHB. Eleven (38%) and 18 pts (62%) received MHB as adjuvant or definitive treatment respectively. Five-year LRFS, RRFS, MFS, SS and OS were 82%, 82%, 89%, 88% and 73% respectively. Six patients (20.7%) experienced local relapse and underwent salvage penectomy leading to a penile preservation rate of 79.3%. Acute skin toxicity was reported 1 month after MHB, with 28% G1, 66% G2 and 6% G3. Late skin complications were telangiectasia for 5 pts (17%) and necrosis for 3 pts (10.3% requiring hyperbaric oxygen therapy). Comparing pre- and post-treatment status, no significant change was observed for skin appearance, IPSS and IIEF-5. Conclusion MHB represents an efficient first line conservative treatment option for early penile cancers. Oncological outcome and late toxicity profile appear encouraging. However, larger-scale cohorts with longer follow-up are needed to more accurately precise the features of the best candidate to MHB.

Objectives The SiFEBI trial demonstrated that a post-operative Multicatheter Interstitial Brachytherapy (MIB) appears feasible and with acceptable toxicity in older adults aged 70 years and older presenting with low-risk breast cancer. The aim of the present ancillary study was to analyze the quality of life and Comprehensive Geriatric Assessment (CGA) domains within 6 months in older adults receiving Accelerated Partial Breast Irradiation (APBI) using a single fraction of MIB. Materials and Methods From 11/2012 to 09/2014, 37 patients were included and 26 were evaluable. Patients (pts) aged 70 years and older with a Balducci score of 1 or 2 and presenting with low-risk breast cancer were prospectively enrolled in this phase I/II trial ( NCT01727011 ). After lumpectomy, intra-operative catheter implantation was performed for post-operative APBI after pathological findings. Quality of life (QoL) evaluation and CGA were scheduled at baseline and 1, 3, and 6 months after APBI. Autonomy decline was defined as a 1-point decrease in Activities of Daily Living (ADL). Results Mean age was 77 years. Within the first 6 months of follow-up, no autonomy decline was observed in ADL, 3 patients had an autonomy decline in Instrumental Activities of Daily Living (IADL) and 2 patients had a slower gait speed but no changes in cognitive function, nutritional status, and depression screening. Global QoL was quite similar at baseline compared to 1, 3, and 6 months. No differences were observed for functional items. Conclusion APBI based on a single fraction of MIB in older adults with low-risk breast cancer appears to be feasible with a minimal loss of autonomy regarding IADL, no loss of autonomy in ADL, an acceptable decrease in other CGA domains, and with no impact on global quality of life.

Resume La castration chirurgicale ou chimique, en particulier avec les analogues de la LH-RH utilises lors du cancer de la prostate est responsable d’une perte osseuse importante et rapide. Cette perte osseuse est due a la diminution de la testosteronemie, et peut-etre a l’origine d’une augmentation du risque de fractures. L’objectif de ces recommandations est de proposer, a la suite d’une revue de la litterature, une attitude consensuelle pratique pour la prevention et le traitement de l’osteoporose chez ces patients, entre les differentes societes savantes qui ont participe a ce travail : Societe francaise de rhumatologie (SFR), Groupe de recherche et d’information sur les osteoporoses (GRIO), Groupe europeen d’etudes des metastases osseuses (GEMO), Association francophone pour les soins de support (AFSOS), Association francaise d’urologie (AFU), Societe francaise de radiotherapie oncologique (SFRO), en tenant compte des modalites de prescription et de remboursement des traitements en France. Il est recommande que tous ces patients aient une evaluation du risque de fracture et une prevention des facteurs de risque de perte osseuse. Il est recommande que les patients aux antecedents de fracture osteoporotique severe et/ou ayant un T-score

Brachytherapy boost after external beam radiotherapy for intermediate and high-risk prostate cancer is presented as an attractive technique in numerous retrospective and prospective studies. Currently, three randomized controlled trials comparing brachytherapy versus external beam radiotherapy boost used non-homogenous irradiation features. Therefore, we analyzed the oncological outcomes by a systematic review with meta-analysis of the randomized controlled trials.We performed a systematic literature review of MEDLINE and COCHRANE databases up to 30/04/10 and we considered all published randomized controlled trials comparing brachytherapy versus external beam radiotherapy boost for intermediate and high-risk prostate cancer according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. The review was assessed using Assessing the Methodological Quality of Systematic Reviews (AMSTAR) tool and the identified reports were reviewed according to the Consolidated Standards of Reporting Trials (CONSORT). Eight publications from 3 RCTs were selected.There was a significant benefit in 5-year biochemical-progression-free survival in favor of BT versus EBRT boost (HR: 0.49 [95% CI, 0.37-0.66], p 0.01). There was no difference at 5 years in overall survival (HR: 0.92 [95% CI, 0.64-1.33], p = 0.65), ≥ grade 3 late genito-urinary (RR: 2.19 [95%CI, 0.76-6.30], p = 0.15) and late gastro-intestinal toxicities (RR: 1.85 [95%CI, 1.00-3.41] p = 0.05).This meta-analysis provides further evidence in favor of BT boost for intermediate and high-risk prostate cancer in terms of b-PFS improvement, leading to suggest BT boost as level I and grade A recommendation. However, the risk of grade ≥ 3 late toxicity must be carefully investigated.

Introduction et but de l’etude L’escalade de dose de radiotherapie dans les cancers de prostate de risque intermediaire ou haut risque ameliore le controle biochimique. Le complement en curietherapie qui permet de delivrer une dose elevee, a montre dans trois essais randomises un benefice superieur par rapport a la radiotherapie seule. Le groupe curietherapie de la Societe francaise de radiotherapie oncologique (SFRO) a conduit une etude retrospective multicentrique pour rapporter des donnees d’efficacite et de tolerance du complement en curietherapie en vie reelle. Materiel et methodes une etude retrospective multicentrique a ete conduite, incluant la totalite des patients consecutifs atteints de cancer de prostate de risque intermediaire ou haut risque pris en charge par association de radiotherapie externe et de boost par curietherapie, qu’elle soit par haut debit de dose ou par implants permanents de grains d’iode 125, de 2006 jusqu’en decembre 2019. Les caracteristiques des patients, de la maladie initiale, des traitements et du suivi ont ete recueillies. Resultats et analyse statistique Mille treize patients ont ete inclus (dont 960 pris en charge apres 2010) ; 914 patients ont ete suivis et leurs resultats analyses, dont 864 ayant recu une curietherapie de haut debit de dose (dose mediane 14 Gy en une fraction) et 50 par implants permanents de grains d’iode 125 (dose mediane 110 Gy). Quatre-cent-vingt-quatre cancers etaient de risque intermediaire et 490 de haut risque. La dose mediane de radiotherapie externe etait de 46 Gy. Apres un suivi median de 63 mois, le controle biochimique a 5 ans etait de 90 % pour la population globale, 94 % et 86 % pour les cancers de risque intermediaire ou haut risque, respectivement. A 5 ans, les taux de survie sans rechute biochimique ni clinique, survie sans metastase et controle local etaient respectivement de 67 %, 92 % et 97 %. Une toxicite tardive de grade 2 ou plus etait retrouvee chez 70 patients (soit 7,7 %) et 18 patients (soit 2 %) sur les plans urinaire et digestif. Conclusion Cette etude multicentrique montre l’efficacite de l’association de la curietherapie en complement de la radiotherapie externe et sa bonne tolerance. Cette base de donnees, en cours d’enrichissement, montre le dynamisme du groupe curietherapie de la SFRO et permettra de mieux etudier les facteurs influencant le controle du cancer de prostate et de contribuer a la diffusion de cette technique sur le territoire national.

Purpose Regarding adjuvant radiation therapy making decision for elderly women, Albert (2013) published a nomogram predicting the mastectomy-free survival (MFS) rate with or without adjuvant irradiation. Based on this approach, we proposed to investigate the use of accelerated partial breast irradiation (APBI) vs. whole breast irradiation (WBI) or endocrine therapy alone in elderly low-risk breast cancer patients. Methods and Materials For each elderly woman treated by conserving surgery and APBI (multicatheter interstitial high-dose-rate brachytherapy), 5- and 10-year MFS rates were calculated. For each treated patient, using the Albert nomogram, we calculated the estimated MFS rates at 5 and 10 years, with and without WBI. Then, we compared the estimated MFS rates after no irradiation and WBI vs. observed MFS rates after APBI. Results From 2005 to 2016, 79 patients were treated. Median followup was 96.8 months [68.6–104.9], median age was 77 years [66–89]. Expected 5- and 10-year mastectomy rates calculated with the Albert nomogram without WBI were 2.95% and 7.25%, respectively, leading to a 10-year MFS rate of 92.7%. Expected 5- and 10-year mastectomy rates after WBI were 1.41% and 3.66%, respectively, leading to a 10-year MFS rate of 96.3%. Regarding observed MFS rate, 1 pt (1.3%) experienced a salvage mastectomy. The 10-year MFS rate after APBI was 97.4% vs. 96.3% after WBI ( p = 1) and 92.7% after no irradiation ( p = 0.27). No toxicity Grade 3 or more was observed. Conclusions APBI seems to be an attractive compromise between WBI and no irradiation for elderly women with early stage breast cancer as far as local control, quality of life and cost benefit is concerned.

Introduction et but de l’etude Les recommandations de la medecine par les preuves reposent sur 5 % des donnees medicales, essentiellement issues des essais cliniques. Les 95 % restantes dites de “vie reelle” restent largement inexploitees alors qu’elles peuvent completer les connaissances. Nous rapportons ici une adaptation libre et gratuite d’un logiciel de radiotherapie (Mosaiq®) permettant d’enregistrer et de restituer les donnees issues des soins courant en radiotherapie. Cette production de donnees est « structuree », c’est-a-dire creee et restituee dans un format directement exploitable pour la recherche. Cette adaptation est progressivement utilisee par cinq centres et permet un partage multicentrique des donnees. Materiel et methodes En 2016 un parametrage comprenant 37 formulaires de types e-CRF (electronic case report form) utilises en consultation a ete defini puis synchronise entre les centres. Ces formulaires sont adaptes aux tumeurs et a la prise en charge pour un usage quotidien. Leur utilisation permet la saisie des donnees structurees au fil de la consultation et leur ergonomie associee a des courriers automatises permet une baisse de la charge de travail des medecins. Une copie hebdomadaire de 421 elements pertinents est realisee de Mosaiq® vers une base de donnees relationnelle. Ces elements couvrent le traitement (doses, seances, etc.), la tumeur (CIM10, etc.) et les donnees des formulaires (toxicite selon les Common Terminology Criteria for Adverse Events [CTCAE], controle tumoral). Ces outils en production dans cinq etablissements permettent une production continue de donnees. Les bases de donnees relationnelles sont securisees, accessibles uniquement dans l’etablissement et ne communiquent pas entre elles. Cependant, leur structure identique permet une analyse par une seule requete informatique appliquee localement, et valable pour tous les centres avec un cout en ressource infime. Le resultat d’une requete peut etre ensuite analyse localement ou partage avec une autre equipe pour un projet de recherche en respectant le reglement general sur la protection des donnees (RGPD). Une documentation de la structure des bases de donnees relationnelles permet leur exploitation par des personnes sans formation en oncologie. Resultats et analyse statistique Plusieurs requetes ont ete creees a l’Icans (Unicancer Strasbourg) et appliquees en fevrier 2020 dans les instituts Jean-Godinot, Gustave-Roussy, Antoine-Lacassagne et Oscar-Lambret sans mobilisation de ressources humaines informatiques locales. Les fichiers Excel® des resultats sont automatiquement mis a jour toutes les semaines. Le partage puis l’analyse des resultats a montre que les cas de 11343 patients ont ete evalues lors de 50374 consultations. Deux etudes « preuve de concept » sur les traitements mammaires portant sur 2991 patientes ont ete realisees et publiees (Societe francaise de radiotherapie oncologique [SFRO] en 2019, European Society for Radiotherapy and Oncology [ESTRO] en 2020). Conclusion L’adaptation d’un logiciel de radiotherapie pour recueillir et mettre a disposition les donnees de vie reelle est possible. Leur exploitation multicentrique a faible cout ouvre de nouveaux horizons pour la recherche et viendra completer les connaissances. Cette production quotidienne constitue le socle d’etudes en cours dans les centres participants.