Postoperative Outcomes of Pre-Pectoral Versus Sub-Pectoral Implant Immediate Breast Reconstruction.

INTRODUCTION: Immediate breast reconstruction (IBR) techniques are rapidly evolving. We compared the results from a single-center implant IBR cohort between subpectoral and prepectoral implants with and without a mesh. METHODS: We analyzed all complications and grade 2-3 complications, the implant loss rate, the surgery time, the length of stay (LOS), patient satisfaction, the interval time to adjuvant therapy and cost, with a comparison between subpectoral and prepectoral implant IBR. RESULTS: Subpectoral implant IBR was carried out in 529 mastectomies (62.0%) and prepectoral in 324, with a significant increase in prepectoral placement in recent years. Mesh was used in 176 prepectoral placements (54.3%). Any grade of complication was reported in 147 mastectomies (17.2%), with a significantly higher rate for prepectoral implant IBR (p = 0.036). Regression analysis showed that prepectoral implant was not significantly associated with any grade of complication or with grade 2-3 complications. Prepectoral implant IBR was associated with a significantly shorter operative time and lower LOS. Grade 2-3 complications were significantly associated with lower satisfaction. Higher costs were significantly associated with the subpectoral placement and mesh. A complication rate predictive score identified five groups with a significant increase in grade 2-3 complications. CONCLUSIONS: Prepectoral-M-IBR increased over time with no difference in complication rates compared to subpectoral-M-IBR. Prepectoral implant placement can be considered a safe technique.

Does Breast Surgery Type Alter Incidental Axillary Irradiation? A Dosimetric Analysis of the "Sentinel Envahi et Randomisation du Curage" SERC Trial.

BACKGROUND: An incidental axillary dose of adjuvant radiotherapy using tangential beams is usually given after breast-conserving surgery for breast cancer. The goal of this sub-study was to evaluate this incidental dose in the setting of post-mastectomy radiotherapy (PMRT) according to two different radiotherapy techniques. METHODS: Patients participating in a randomized SERC trial who received PMRT in a single center were included. We collected the incidental axillary dose delivered to the Berg level 1 using different dosimetric parameters and compared two techniques using Student's t-test: three-dimensional conformal radiotherapy (3D-CRT) and volumetric arc therapy (VMAT). RESULTS: We analyzed radiotherapy plans from 52 patients who received PMRT from 2012 to 2021. The mean dose delivered to the Berg level 1 was 37.2 Gy. It was significantly higher with VMAT than with 3D-CRT-43.6 Gy (SD = 3.1 Gy) versus 34.8 Gy (SD = 8.6 Gy) p < 0.001. Eighty-four percent of the Berg level 1 was covered by 40 Gy isodose in the VMAT group versus 55.5% in the 3D-CRT group p < 0.001. CONCLUSIONS: On the Berg level 1, PMRT gives a dose at least equivalent to the one given by post-breast-conserving surgery radiotherapy, making it possible to limit completion axillary lymph node dissections in select pN1a patients treated with a mastectomy. Modern radiotherapy techniques like VMAT tend to increase this incidental dose.

Neoadjuvant chemotherapy for breast cancer: Pathologic response rates but not tumor size, has an independent prognostic impact on survival.

AIM: We investigated the pathologic complete response rates (pCR) and survival outcomes of early breast cancer patients who underwent neoadjuvant chemotherapy (NAC) over 14 years at a French comprehensive cancer center and reported pCR and survival outcomes by tumor subtypes and size. METHODS: From January 2005 to December 2018, 1150 patients receiving NAC were identified. Correlations between cT stage, breast tumor response, axillary lymph node response, pCR, surgery, and outcomes were assessed. pCR was defined as (ypT0/ypTis) and (ypN0/pN0sn). RESULTS: A pCR was reached in 31.7% (365/1150) of patients and was strongly associated with tumor subtypes, but not with tumor size (pretreatment cT category). Luminal-B Her2-negative and triple-negative (TN) subtypes, cN1 status, older age, and no-pCR had an independent negative prognostic value. Overall survival (OS), relapse-free survival (RFS), and metastasis-free survival (MFS) were not significantly different for cT0-1 compared to cT2 stages. In Cox-model adjusted on in-breast pCR and pN status, ypN1 had a strong negative impact (OS, RFS, and MFS: HR = 3.153, 4.677, and 6.133, respectively), higher than no in-breast pCR (HR = 2.369, 2.252, and 2.323). A negative impact of no pCR on OS was observed for cN0 patients and TN tumors (HR = 4.972) or HER2-positive tumors (HR = 11.706), as well as in Luminal-B Her2-negative tumors on MFS (HR = 2.223) and for Luminal-A on RFS (HR = 4.465) and MFS (HR = 4.185). CONCLUSION: Achievement of pCR, but not tumor size (pretreatment cT category), has an independent prognostic impact on survival. These results suggest potential NAC benefits in patients with small tumors (<2 cm), even in absence of clinically suspicious lymph nodes. Residual lymph node disease after NAC is the most powerful adverse prognostic factor.

A novel lung SBRT treatment planning: Inverse VMAT plan with leaf motion limitation to ensure the irradiation reproducibility of a moving target.

This study exposed the implementation of a novel technique (VMATLSL) for the planning of moving targets in lung stereotactic body radiation therapy (SBRT). This new technique has been compared to static conformal radiotherapy (3D-CRT), volumetric-modulated arc therapy (VMAT) and dynamic conformal arc (DCA). The rationale of this study was to lower geometric complexity (54.9% lower than full VMAT) and hence ensure the reproducibility of the treatment delivery by reducing the risk for interplay errors induced by respiratory motion. Dosimetry metrics were studied with a cohort of 30 patients. Our results showed that leaf speed limitation provided conformal number (CN) close to the VMAT (median CN of VMATLSL is 0.78 vs 0.82 for full VMAT) and were a significant improvement on 3D-CRT and DCA with segment-weight optimized (respectively 0.55 and 0.57). This novel technique is an alternative to VMAT or DCA for lung SBRT treatments, combining independence from the patient's breathing pattern, from the size and amplitude of the lesion, free from interplay effect and with dosimetry metrics close to the best that could be achieve with full VMAT.

Dosimetric comparison of VMAT standard optimization (SO) and multi-criteria optimization (MCO) treatment plans with standard mode delivery (STD) or sliding window (SW) for head and neck cancer.

PURPOSE: A new development on the RayStation treatment planning system (TPS) allows a plan to be planned by imposing a constraint on the leaf sequencing: all leaves move in the same direction before moving again in the opposite direction to create a succession of sliding windows (SWs). The study aims to investigate this new leaf sequencing, coupled with standard optimization (SO) and multi-criteria optimization (MCO) and to compare it with the standard sequencing (STD). METHODS: Sixty plans were replanned for 10 head and neck cancer patients (two dose levels simultaneously SIB, 56 and 70 Gy in 35 fractions). All plans were compared, and a Wilcoxon signed-rank test was performed. Pre-processing QA and metrics of multileaf collimator (MLC) complexity were studied. RESULTS: All methodologies met the dose requirements for the planning target volumes (PTVs) and organs at risk (OARs). SO demonstrates significantly best results for homogeneity index (HI), conformity index (CI), and target coverage (TC). SO-SW gives best results for PTVs (D98% and D2% ) but the differences between techniques are less than 1%. Only the D2%,PTV-56 Gy is higher with both MCO methods. MCO-STD offer the best sparing OARs (parotids, spinal cord, larynx, oral cavity). The gamma passing rates (GPRs) with 3%/3 mm criteria between the measured and calculated dose distributions are higher than 95%, slightly lowest with SW. The number of monitor units (MUs) and MLC metrics are higher in SW show a higher modulation. CONCLUSIONS: All plans are feasible for the treatment. A clear advantage of SO-SW is that the treatment plan is more straightforward to planning by the user due to the more advanced modulation. MCO stands out for its ease of use and will allow a less experienced user to offer a better plan than in SO. In addition, MCO-STD will reduce the dose to the OARs while maintaining good TC.

The impact of brachytherapy boost for anal canal cancers in the era of de-escalation treatments.

PURPOSE: To analyze clinical outcomes of high-dose-rate (HDR) interstitial brachytherapy boost (ISBT) after external beam radiation therapy (EBRT) or chemoradiotherapy (CRT) for the treatment of anal canal cancers (ACC). METHODS AND MATERIALS: A total of 78 patients with ACC were treated at our institution by ISBT. Local Control (LC), disease-free survival (DFS), overall survival (OS), colostomy-free survival (CFS) and toxicity rates were analyzed. RESULTS: With a median followup (FU) of 59.8 months (95% CI [55.8-64.2]), six (7.7%) local recurrences with 2 patients (2.6%) having persistent disease at 3 months were observed. The 5-year rate of LC for the entire population was 92% [83-96%]. The 5-year DFS rate was 86% [76-93%]. The 5-year OS was 96% [88-99%]. In the univariate analysis, chemotherapy was significantly associated with morbidity grade ≥2. Late digestive toxicity grade ≥3 was reported in 8.9% patients, 1 patient underwent colostomy due to toxicity. The 5-year CFS rate was 88% [79-94%]. CONCLUSIONS: HDR interstitial brachytherapy boost provide excellent rates of tumor control and colostomy-free survival with a favorable profile of GI toxicity. Continence in anal cancer survivors is a challenge and the boost technique must be discussed in a multidisciplinary approach as part of de-escalation treatments.

Is MRI-Linac helpful in SABR treatments for liver cancer?

Objective: To determine the MRI-Linac added value over conventional image-guided radiation therapy (IGRT) in liver tumors Stereotactic ablative radiation therapy (SABR). Materials and methods: We retrospectively compared the Planning Target Volumes (PTVs), the spared healthy liver parenchyma volumes, the Treatment Planning System (TPS) and machine performances, and the patients' outcomes when using either a conventional accelerator (Versa HD®, Elekta, Utrecht, NL) with Cone Beam CT as the IGRT tool or an MR-Linac system (MRIdian®, ViewRay, CA). Results: From November 2014 to February 2020, 59 patients received a SABR treatment (45 and 19 patients in the Linac and MR-Linac group, respectively) for 64 primary or secondary liver tumors. The mean tumor size was superior in the MR-Linac group (37,91cc vs. 20.86cc). PTV margins led to a median 74%- and 60% increase in target volume in Linac-based and MRI-Linac-based treatments, respectively. Liver tumor boundaries were visible in 0% and 72% of the cases when using CBCT and MRI as IGRT tools, respectively. The mean prescribed dose was similar in the two patient groups. Local tumor control was 76.6%, whereas 23.4% of patients experienced local progression (24.4% and 21.1% of patients treated on the conventional Linac and the MRIdian system, respectively). SABR was well tolerated in both groups, and margins reduction and the use of gating prevented ulcerous disease occurrence. Conclusion: The use of MRI as IGRT allows for the reduction of the amount of healthy liver parenchyma irradiated without any decrease of the tumor control rate, which would be helpful for dose escalation or subsequent liver tumor irradiation if needed.

Physicians' Opinion on Intraoperative Radiotherapy as a Therapeutic De-Escalation Option in Older Women with Early Breast Cancer.

BACKGROUND: Intraoperative radiotherapy (IORT) is a therapeutic de-escalation option in older women with low-risk early breast cancer (EBC). A qualitative study was implemented to describe EBC physicians' points of view on IORT as a de-escalation option. METHODS: Recorded face-to-face and telephone semi-structured interviews were conducted among diverse physicians from seven French comprehensive cancer centers. Interview transcripts were grouped as corpus to construct a typology. Thematic analysis was performed. RESULTS: Positions toward IORT were contrasted between the 16 participating physicians. Five fully supported IORT as a de-escalation option, four were not in favor, and seven had a more reserved or neutral opinion. Points of divergence concerned treatment efficacy, treatment duration, side effects and sequelae, psychological impact, compliance with adjuvant endocrine therapy, logistical constraints, financial cost, and availability of other techniques of partial breast irradiation. Physicians in favor of IORT emphasized direct benefits for the patient, and those against pointed the lack of specific guidelines, risk of lost opportunity in older women with long life expectancy, and challenges of shared decision making. CONCLUSIONS: Despite national policies to preserve cancer patients' quality of life and increase their participation in medical decision making, therapeutic de-escalation using IORT is not consensual among physicians. Further efforts are needed to promote patient-centered care.

Triple-negative and Her2-positive breast cancer in women aged 70 and over: prognostic impact of age according to treatment.

Background: Elderly breast cancer (BC) patients have been underrepresented in clinical trials whereas ~60% of deaths from BC occur in women aged 70 years and older. Only limited data are available on the prognostic impact of age according to treatment, especially in the triple-negative (TN) and Her2-positive because of the lower frequency of these subtypes in elderly patients. We report herein the results of a multicenter retrospective study analyzing the prognostic impact of age according to treatment delivered in TN and Her2-positive BC patients of 70 years or older, including comparison by age groups. Methods: The medical records of 31,473 patients treated from January 1991 to December 2018 were retrieved from 13 French cancer centers for retrospective analysis. Our study population included all ≥70 patients with TN or Her2-positive BC treated by upfront surgery. Three age categories were determined: 70-74, 75-80, and > 80 years. Results: Of 528 patients included, 243 patients were 70-74 years old (46%), 172 were 75-80 years (32.6%) and 113 were >80 years (21.4%). Half the population (51.9%, 274 patients) were TN, 30.1% (159) Her2-positive/hormone receptors (HR)-positive, and, 18% (95) Her2-positive/endocrine receptors (ER)-negative BC. Advanced tumor stage was associated with older age but no other prognostic factors (tumor subtype, tumor grade, LVI). Adjuvant chemotherapy delivery was inversely proportional to age. With 49 months median follow-up, all patient outcomes (overall survival (OS), disease-free survival (DFS), breast cancer-specific survival (BCSS), and recurrence-free survival (RFS)) significantly decreased as age increased. In multivariate analysis, age >80, pT2-3 sizes, axillary macrometastases, lymphovascular involvement, and HR-negativity tumor negatively affected DFS and OS. Comparison between age >80 and <=80 years old showed worse RFS in patients aged > 80 (HR=1.771, p=0.031). Conclusion: TN and Her2-positive subtypes occur at similar frequency in elderly patients. Older age is associated with more advanced tumor stage presentation. Chemotherapy use decreases with older age without worse other pejorative prognostic factors. Age >80, but not ≤80, independently affected DFS and OS.

Mastectomy and Immediate Breast Reconstruction with Pre-Pectoral or Sub-Pectoral Implant: Assessing Clinical Practice, Post-Surgical Outcomes, Patient's Satisfaction and Cost.

Immediate breast reconstruction (IBR) rates increase during last years and implant-based reconstruction was the most commonly performed procedure. We examined data collected over 25 months to assess complication rate, duration of surgery, patient's satisfaction and cost, according to pre-pectoral or sub-pectoral implant-IBR. All patients who received an implant-IBR, from January 2020 to January 2022, were included. Results were compared between pre-pectoral and sub-pectoral implant-IBR in univariate and multivariate analysis. We performed 316 implant-IBR, 218 sub-pectoral and 98 (31%) pre-pectoral. Pre-pectoral implant-IBR was significantly associated with the year (2021: OR=12.08 and 2022: OR=76.6), the surgeons and type of mastectomy (SSM vs NSM: OR=0.377). Complications and complications Grade 2-3 rates were 12.9% and 10.1% for sub-pectoral implant-IBR respectively, without significant difference with pre-pectoral implant-IBR: 17.3% and 13.2%. Complications Grade 2-3 were significantly associated with age <50-years (OR=2.27), ASA-2 status (OR=3.63) and cup-size >C (OR=3.08), without difference between pre and sub-pectoral implant-IBR. Durations of surgery were significantly associated with cup-size C and >C (OR=1.72 and 2.80), with sentinel lymph-node biopsy and axillary dissection (OR=3.66 and 9.59) and with sub-pectoral implant-IBR (OR=2.088). Median hospitalization stay was 1 day, without difference between pre and sub-pectoral implant-IBR. Cost of surgery was significantly associated with cup-size > C (OR=2.216) and pre-pectoral implant-IBR (OR=8.02). Bad-medium satisfaction and IBR-failure were significantly associated with local recurrence (OR=8.820), post-mastectomy radiotherapy (OR=1.904) and sub-pectoral implant-IBR (OR=2.098). Conclusion: Complications were not different between pre and sub-pectoral implant-IBR. Pre-pectoral implant-IBR seems a reliable and faster technique with better patient satisfaction but with higher cost.

Impact of fiducial markers placement on the delineation of target volumes in radiation therapy for oesophageal cancer: FIDUCOR study.

Purpose: This prospective monocentric phase II study (FIDUCOR-study, NCT02526134) aimed to assess the impact of fiducial markers (FMs) implantation on conformal chemo-radiation therapy (CRT) planning in oesophageal carcinoma (EC) patients. Methods/materials: Fifteen EC patients were enrolled in the study. Each patient underwent two simulation CT-scans before (CT1) and after (CT2) FMs implantation, in the same position. FMs (3 mm length gold markers, preloaded in a 22G needle) were implanted after sedation, under endoscopic ultrasound (EUS) and X-Ray guidance, and were placed at the tumor's extremities, and in the visible lymph nodes. Target delineation and treatment plan were both performed first on CT1 with the assistance of diagnosis CT, gastroscopy and EUS details, and second on CT2 using FMs and CT-data. The value of FMs implantation was assessed by the difference of growth-tumor-volume (GTV) and clinical-target-volume (CTV) between CT1-based and CT2-based delineation. A significant difference was defined as a ≥5 mm-difference on axial(x) or coronal(y) slices, a ≥10mm-difference on sagittal slices, or a ≥20%-difference in GTV. The impact on dose distribution in organs at risk (OAR) (lung, heart, liver) was also studied. Results: Between 09/2014 and 12/2015, 15 patients could achieve fiducial procedures, without any complication. One FM migration occurred. We observed a significant modification of the GTV-dimension in 100% of the cases (15/15, 95%CI: [78.2;100.0]), mainly due to a difference in sagittal dimension with a mean variation of 11.2 mm and a difference> 10 mm for 8/15 patients (53.3%). One patient had a significant isocenter displacement as high as 20 mm. The oesophagus tumor was not seen on the CT-scan in one patient due to its small size. One patient had a distant lymph node metastasis not visible on CT-scan. We observed no significant impact on OAR distribution. Conclusion: In our study, FMs-implantation under EUS had a positive impact on accurate volume definition in EC-patients (modification of GTV in 15/15 patients). Close cooperation between gastroenterologist and radiation oncologist has the potential to improve local treatment of oesophageal carcinoma.

Early clinical outcomes of hybrid brachytherapy for locally advanced cervical cancer: making adverse situations in a favorable scenario.

Purpose: To investigate the feasibility and early clinical outcomes of combined intra-cavitary (IC) and interstitial (IS) image-guided adaptive brachytherapy (IGABT) as curative and definitive treatment of patients treated with chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC). Material and methods: Data from medical records of all consecutive patients with histologically proven cervical cancer (FIGO 2018 stage IB-IV), treated by brachytherapy after CCRT at our institution between 2017 and 2020 were reviewed. Results: One hundred and forty-two patients with LACC FIGO 2018 stages (IB: 20.4%, II: 31.7%, III: 45.8%, IV: 2.1%) underwent brachytherapy at our institution, out of which 53.5% underwent combined brachytherapy technique (IC/IS). Median number of implanted catheters was 3 (range, 1-6 catheters). None of the 142 patients required invasive hemorrhage management. With a median follow-up of 21.6 (95% CI [confidence interval]: 19.1-23.5%) months, local relapse was observed in nine patients (6.3%), with four showing persistent and progressive disease. The estimated 2-year local and pelvic relapse-free survival were 92% (95% CI: 84-96%) and 90% (95% CI: 83-94%), respectively. The estimated 2-year disease-free survival for the entire population was 80% (95% CI: 71-87%). The 2-year overall survival (OS) rate for the entire population was 92% (95% CI: 84-96%). Acute toxicity G3 was reported in two (1.4%) patients. High-grade late toxicity (grade 3) was reported in 9 (6.3%) patients. Conclusions: Combined IC/IS brachytherapy for LACC allows for recommended doses to achieve local control even in large tumors after CCRT improving target volume coverage, with low rates of acute morbidity. Hybrid brachytherapy technique (IC/IS) is essential to have a favorable scenario at the time of brachytherapy to correctly treat locally advanced cervical cancer patients.

Adaptive Magnetic Resonance-Guided External Beam Radiation Therapy for Consolidation in Recurrent Cervical Cancer.

Purpose: Adaptive magnetic resonance (MR)-guided brachytherapy takes an important place as consolidation within the care of cervical malignancies, but may be impracticable in some unusual cases. This work aimed to present the case of adaptive MR-guided external beam radiation therapy (aMRgRT) used as a boost in a recurrence of cervical cancer. Methods and Materials: We report on a case of a parametrial recurrence in a 31-year-old patient who already underwent a trachelectomy as treatment for her primary growth. After concomitant radio-chemotherapy, a brachytherapy boost was performed. Because of its position in relation to the left uterine artery after trachelectomy, impeding interstitial catheters set up, the relapse was insufficiently covered. With the aim to refine the coverage of target volumes, aMRgRT treatment was undertaken to allow for achievement of the dosimetric goals. Results: In clinical circumstances where the brachytherapy step was hindered, aMRgRT presents many advantages. First, daily native MR-imaging outperforms usual x-ray imaging in the pelvis, refining repositioning. Second, its specific workflow allows for the performance of adaptive treatment, with consideration of both the inter- and intrafraction motions of organs at risk and target volumes. Conclusion: In nonfeasible brachytherapy situations, aMRgRT could be a satisfying substitute. Nevertheless, brachytherapy remains the standard of care as a boost in locally advanced cervical cancer.

Clinical adoption patterns of 0.35 Tesla MR-guided radiation therapy in Europe and Asia.

BACKGROUND: Magnetic resonance-guided radiotherapy (MRgRT) utilization is rapidly expanding, driven by advanced capabilities including better soft tissue imaging, continuous intrafraction target visualization, automatic triggered beam delivery, and the availability of on-table adaptive replanning. Our objective was to describe patterns of 0.35 Tesla (T)-MRgRT utilization in Europe and Asia among early adopters of this novel technology. METHODS: Anonymized administrative data from all 0.35T-MRgRT treatment systems in Europe and Asia were extracted for patients who completed treatment from 2015 to 2020. Detailed treatment information was analyzed for all MR-linear accelerators (linac) and -cobalt systems. RESULTS: From 2015 through the end of 2020, there were 5796 completed treatment courses delivered in 46,389 individual fractions. 23.5% of fractions were adapted. Ultra-hypofractionated (UHfx) dose schedules (1-5 fractions) were delivered for 63.5% of courses, with 57.8% of UHfx fractions adapted on-table. The most commonly treated tumor types were prostate (23.5%), liver (14.5%), lung (12.3%), pancreas (11.2%), and breast (8.0%), with increasing compound annual growth rates (CAGRs) in numbers of courses from 2015 through 2020 (pancreas: 157.1%; prostate: 120.9%; lung: 136.0%; liver: 134.2%). CONCLUSIONS: This is the first comprehensive study reporting patterns of utilization among early adopters of a 0.35T-MRgRT system in Europe and Asia. Intrafraction MR image-guidance, advanced motion management, and increasing adoption of on-table adaptive RT have accelerated a transition to UHfx regimens. MRgRT has been predominantly used to treat tumors in the upper abdomen, pelvis and lungs, and increasingly with adaptive replanning, which is a radical departure from legacy radiotherapy practices.

Lived experience and perceived advantages of therapeutic De-escalation: A qualitative study of older patients with breast cancer.

INTRODUCTION: One option for therapeutic de-escalation in older women with early breast cancer (EBC) is partial breast irradiation (PBI) instead of whole-breast irradiation (WBI) when the latter has no clear advantages. We aimed to explore the decision-making processes and the lived experiences of WBI and PBI from the perspectives of older women with EBC. MATERIALS AND METHODS: Thematic content analysis was performed on qualitative data collected using narrative interviews. RESULTS: Twenty-two women aged 65 and over participated (ten patients who underwent WBI and twelve who underwent PBI). We identified three themes from their narratives: 1) Acceptance of a paternalistic relationship with physicians, 2) Strong need for an informed choice, and 3) PBI can help people conceal cancer-related physical marks. Narratives underlined participants' preferences for each of the two treatments and their perceptions about therapeutic de-escalation. Misconceptions about therapeutic de-escalation were observed. DISCUSSION: When providing information about EBC treatment options, patients' perceived burden of side effects should be considered. Moreover, eliciting the value older patients place on available breast cancer treatments, as well as their related goals and preferences, could foster their participation in the therapeutic de-escalation decision-making process.

The Management of a Comprehensive Cancer Center during the First Six Months of the COVID-19 Pandemic in the South of France: Lessons from the Paoli-Calmettes Institute's Experience.

During the COVID-19 pandemic, it was rapidly established that cancer patients have an increased risk of developing severe forms of the 2019 coronavirus disease (COVID-19) due to a backlog of cancer diagnostics and immunosuppressive treatments. Cancer centers had to quickly adapt to continue cancer therapies despite the high infection risks and major disruptions in the French healthcare system. We described and analyzed the impact of the pandemic in our institution: management adjustments, COVID-19 infection rates in patients and staff, and impacts on clinical activities and finances during the first wave of the pandemic from March to September 2020. We also compared the results to the clinical activity data from preceding periods. A crisis unit was rapidly created that met 27 times over 66 days, generating numerous changes in hospital protocol. While our area was devastated by the pandemic, the infection rate of our staff and patients remained low (less than 1.5% of all employees). However, the lockdown period was accompanied with a reduction of most clinical activities, leading to decreases of 43%, 36%, 36%, 1%, and 10% in surgery, endoscopy, radiotherapy, and in- and out-patient chemotherapy sessions, respectively, with substantial financial loss. Our report highlights the need for the rapid creation, implementation, and adaptation of new protocols during a pandemic's evolution to prevent disease transmission. Lessons from this situation should provide motivation to better prepare for/limit the dismantling of cancer therapies that can dramatically impact patient care and have deleterious consequences on an institution's financial situation.

[Start of activity with the MRIdian® system: The first 200 patients treated at the Institut Paoli-Calmettes]. / Retour d'expérience clinique à propos des 200 premiers patients traités au MRIdian® à l'Institut Paoli-Calmettes.

INTRODUCTION: Several centers have recently been equipped with MRI-guided radiotherapy systems, including the Paoli-Calmettes Institute which was the first French center to start this activity. We report in this article our early experience. METHODS: Data related to patients treated on the MRIdian® (Viewray®) were prospectively collected. Procedures concerning the implementation of the system and internal organizational issues were summarized. RESULTS: Between February 2019 and March 2020, 201 patients were treated: 40% of treatments were normofractionated (n=70) and 60% used hypofractionation (n=105). The reported monthly occupancy rate at one, six and twelve months was 30%, 62%, and 90%. The distribution of normofractionated treatments was dominated by prostatic (29%) and pancreatic (26%) cancers, followed by abdomino-pelvic irradiations for gynecological cancers (12%) or lymph node diseases (12%) and boosts for rectal or vaginal cancers (11%). Regarding treatments with moderate hypofractionation (dose by fraction between 3 and 5Gy), they corresponded mainly to integrated boost for abdomino-pelvic lymph nodes (38%), while the stereotaxic treatments primarily concerned hepatic lesions (15%), bones (30%). DISCUSSION: The MRIdian® was initially used widely in our service corresponding to a learning curve for MRI guidance. This new tool for image-guided radiotherapy helped us to secure our practice providing solutions for both inter and intra-fraction movements making it possible to reduce the additional margin in order to better protect the organs at risk. The main technical difference with conventional accelerators is the possibility of performing adaptive radiotherapy in real time, the start of which was more gradual.

Sentinel node involvement with or without completion axillary lymph node dissection: treatment and pathologic results of randomized SERC trial.

Based on results of clinical trials, completion ALND (cALND) is frequently not performed for patients with breast conservation therapy and one or two involved sentinel nodes (SN) by micro- or macro-metastases. However, there were limitations despite a conclusion of non-inferiority for cALND omission. No trial had included patients with SN macro-metastases and total mastectomy or with >2 SN macro-metastases. The aim of the study was too analyze treatment delivered and pathologic results of patients included in SERC trial. SERC trial is a multicenter randomized non-inferiority phase-3 trial comparing no cALND with cALND in cT0-1-2, cN0 patients with SN ITC (isolated tumor cells) or micro-metastases or macro-metastases, mastectomy or breast conservative surgery. We randomized 1855 patients, 929 to receive cALND and 926 SLNB alone. No significant differences in patient's and tumor characteristics, type of surgery, and adjuvant chemotherapy (AC) were observed between the two arms. Rates of involved SN nodes by ITC, micro-metastases, and macro-metastases were 5.91%, 28.12%, and 65.97%, respectively, without significant difference between two arms for all criteria. In multivariate analysis, two factors were associated with higher positive non-SN rate: no AC versus AC administered after ALND (OR = 3.32, p < 0.0001) and >2 involved SN versus ≤2 (OR = 3.45, p = 0.0258). Crude rates of positive NSN were 17.62% (74/420) and 26.45% (73/276) for patient's eligible and non-eligible to ACOSOG-Z0011 trial. No significant differences in patient's and tumor characteristics and treatment delivered were observed between the two arms. Higher positive-NSN rate was observed for patients with AC performed after ALND (17.65% for SN micro-metastases, 35.22% for SN macro-metastases) in comparison with AC administered before ALND.

Quality assurance program and early toxicities in the phase III BONBIS randomized trial evaluating the role of a localized radiation boost in ductal carcinoma in situ.

PURPOSE: To describe the quality assurance (QA) program and early toxicities in the phase III randomized trial BONBIS (NCT00907868) on the role of a localized radiation boost in ductal carcinoma in situ (DCIS). MATERIALS AND METHODS: From November 2008 to July 2014, 2004 patients were randomized in arm A (only whole breast radiotherapy, WBRT) and arm B (WBRT + boost). The QA program involved 44 participant centers that performed the dummy run (DR). Compliance and uniformity of clinical target volume (CTV) delineations, and dose prescription and delivery according to the BONBIS trial radiotherapy guidelines were analyzed. Acute toxicities (during and up to 3 months after radiotherapy completion, NCI-CTCAE v3.0 classification) were evaluated in 1929 patients. RESULTS: The differences in whole breast CTV (CTV1) and planning target volume (PTV1) were ≤10%, and the differences in boost CTV (CTV2) and PTV (PTV2) were ≥20% compared with the reference DR values; 95% of the prescribed dose encompassed 98.7% and 100% of the median CTV1 and CTV2. Grade ≥2 breast erythema (38.3% vs. 22.4% of grade 2 and 5.4% vs. 2.1% of grade 3, p < 0.001), grade ≥2 dermatitis (2.8% vs. 0.7%, p < 0.001), and grade 2 hyperpigmentation (6.9% vs. 3.6%, p = 0.005) were more frequent in arm B than arm A. No acute lung or cardiac toxicity was observed. Smoking history, large breast size, and large breast CTV were strong predictive factors of grade ≥2 acute skin toxicities. CONCLUSIONS: The QA program showed deviations in breast and tumor bed delineation. The boost significantly increased acute skin toxicities.

Reducing dose to rectum by placement of a rectum-emptying tube in cervical cancer patients treated with brachytherapy.

PURPOSE: Only scarce data are available on the possibility to reduce rectal dose by controlling rectum filling before HDR (high dose rate) IGABT (image-guided adaptive brachytherapy) in LACC (locally advanced cervical carcinoma) patients. We compared dosimetric outcomes before and after the evacuation of gasses using a rectum emptying tube. METHODS AND MATERIAL: Sixty CT (computed tomography) scans from 30 consecutive patients with cancer of the cervix undergoing HDR IGABT after EBRT were reviewed. Patients who underwent at least one gas evacuation were included in the analysis. The three-dimensional dosimetric data of the dosimetric plan performed before and after gas evacuation were compared. Primary endpoint was the difference between D2cc of the rectum before and after the procedure. Expected probability of grade 2-4 overall rectum morbidity was assessed using a probit model from the prospective multicenter EMBRACE study. RESULTS: Thirty five (58.3%) CT scans from 23 patients (76.7%) requiring gas evacuation were analysed. The mean rectum volume, before and after gas evacuation, was 123.1 cc (sd, ± 60.4) and 66.4 cc (sd, ± 34.8), respectively. For each patient, the volume of the rectum after gas evacuation was lower than before. No major complication occurred during and after the procedure. After gas evacuation, a significant reduction in rectal dose per fraction was observed, on average -4.3 Gy (-38.4%, p < 0.001) for D0.1cc and -1.9 Gy (-30.6%, p < 0.001) for D2cc. Estimated mean probability to develop a grade 2-4 rectum morbidity was significantly lower after gas evacuation, 6.9% (sd,± 1.94) versus 9.5% (sd,± 3.17), p < 0.001. CONCLUSION: Gas evacuation using a rectal emptying tube in selected LACC patients treated with HDR BT after chemoradiotherapy, allowed a substantial reduction in the dose to the rectum. Such procedure could be of particular interest when a dose escalation strategy is being considered.