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.

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.

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.

High spatial resolution inorganic scintillator detector for high-energy X-ray beam at small field irradiation.

PURPOSE: Small field dosimetry for radiotherapy is one of the major challenges due to the size of most dosimeters, for example, sufficient spatial resolution, accurate dose distribution and energy dependency of the detector. In this context, the purpose of this research is to develop a small size scintillating detector targeting small field dosimetry and compare its performance with other commercial detectors. METHOD: An inorganic scintillator detector (ISD) of about 200 µm outer diameter was developed and tested through different small field dosimetric characterizations under high-energy photons (6 and 15 MV) delivered by an Elekta Linear Accelerator (LINAC). Percentage depth dose (PDD) and beam profile measurements were compared using dosimeters from PTW namely, microdiamond and PinPoint three-dimensional (PP3D) detector. A background fiber method has been considered to quantitate and eliminate the minimal Cerenkov effect from the total optical signal magnitude. Measurements were performed inside a water phantom under IAEA Technical Reports Series recommendations (IAEA TRS 381 and TRS 483). RESULTS: Small fields ranging from 3 × 3 cm2 , down to 0.5 × 0.5 cm2 were sequentially measured using the ISD and commercial dosimeters, and a good agreement was obtained among all measurements. The result also shows that, scintillating detector has good repeatability and reproducibility of the output signal with maximum deviation of 0.26% and 0.5% respectively. The Full Width Half Maximum (FWHM) was measured 0.55 cm for the smallest available square size field of 0.5 × 0.5 cm2 , where the discrepancy of 0.05 cm is due to the scattering effects inside the water and convolution effect between field and detector geometries. Percentage depth dose factor dependence variation with water depth exhibits nearly the same behavior for all tested detectors. The ISD allows to perform dose measurements at a very high accuracy from low (50 cGy/min) to high dose rates (800 cGy/min) and was found to be independent of dose rate variation. The detection system also showed an excellent linearity with dose; hence, calibration was easily achieved. CONCLUSIONS: The developed detector can be used to accurately measure the delivered dose at small fields during the treatment of small volume tumors. The author's measurement shows that despite using a nonwater-equivalent detector, the detector can be a powerful candidate for beam characterization and quality assurance in, for example, radiosurgery, Intensity-Modulated Radiotherapy (IMRT), and brachytherapy. Our detector can provide real-time dose measurement and good spatial resolution with immediate readout, simplicity, flexibility, and robustness.

Clinical outcome in patients with locally advanced bladder carcinoma treated with conservative multimodality therapy.

OBJECTIVES: To describe the outcome of patients with muscle-invasive bladder carcinoma treated with multimodality therapy in our institution from 1993 to 2002. METHODS: The charts of 60 patients with Stage T2-T4N0-N1M0 treated with transurethral resection of bladder tumor followed by a chemoradiotherapy combination were retrospectively reviewed. Of the 60 patients, 22 had received neoadjuvant chemotherapy (methotrexate, cisplatin, and vinblastine or methotrexate, adriamycin, cisplatin, and vinblastine) followed by concomitant chemoradiotherapy (weekly cisplatin/carboplatin or a cisplatin and 5-fluorouracil combination), and 38 had received concomitant chemoradiotherapy alone. Radiotherapy delivered a median dose of 45 Gy to the pelvis and 65 Gy to the bladder in a once-daily or twice-daily fractionation scheme. Follow-up evaluations included cystoscopy with biopsies at regular intervals. Salvage cystectomy was recommended in the case of local persistent tumor or bladder relapse. RESULTS: The median follow-up was 48.5 months (range 10 to 126). Of the 22 patients who received neoadjuvant chemotherapy, 18 (82%) had received two or more cycles; 51 (85%) of the 60 patients received the concomitant chemotherapy as planned. Radiotherapy was completed in 56 patients. Twenty-eight patients developed relapse either locally (14 did not achieve a complete local response after chemoradiotherapy and 6 had true local relapse during follow-up) or at distant sites. The actuarial 5-year disease-specific survival and freedom from local and distant relapse rate was 54% and 42%, respectively. The actuarial local control rate with an intact bladder was 56% at 5 years. When stratified according to stage and grade, patients with Stage T2-T3, grade 2 tumors had a statistically significantly better chance of remaining relapse free than did the others (P = 0.045). Salvage cystectomy (n = 11) for isolated local failure in this population achieved limited results. CONCLUSIONS: Transurethral resection of bladder tumor with this chemoradiotherapy combination achieved satisfactory results in this unfavorable population with invasive bladder carcinoma.