Biliary tract cancers: French national clinical practice guidelines for diagnosis, treatments and follow-up (TNCD, SNFGE, FFCD, UNICANCER, GERCOR, SFCD, SFED, AFEF, SFRO, SFP, SFR, ACABi, ACHBPT).

INTRODUCTION: This document is a summary of the French intergroup guidelines of the management of biliary tract cancers (BTC) (intrahepatic, perihilar and distal cholangiocarcinomas, and gallbladder carcinomas) published in September 2023, available on the website of the French Society of Gastroenterology (SNFGE) (www.tncd.org). METHODS: This collaborative work was conducted under the auspices of French medical and surgical societies involved in the management of BTC. Recommendations were graded in three categories (A, B and C) according to the level of scientific evidence until August 2023. RESULTS: BTC diagnosis and staging is mainly based on enhanced computed tomography, magnetic resonance imaging and (endoscopic) ultrasound-guided biopsy. Treatment strategy depends on BTC subtype and disease stage. Surgery followed by adjuvant capecitabine is recommended for localised disease. No neoadjuvant treatment is validated to date. Cisplatin-gemcitabine chemotherapy combined to the anti-PD-L1 inhibitor durvalumab is the first-line standard of care for advanced disease. Early systematic tumour molecular profiling is recommended to screen for actionable alterations (IDH1 mutations, FGFR2 rearrangements, HER2 amplification, BRAFV600E mutation, MSI/dMMR status, etc.) and guide subsequent lines of treatment. In the absence of actionable alterations, FOLFOX chemotherapy is the only second-line standard-of-care. No third-line chemotherapy standard is validated to date. CONCLUSION: These guidelines are intended to provide a personalised therapeutic strategy for daily clinical practice. Each individual BTC case should be discussed by a multidisciplinary team.

Dosimetric feasibility of stereotactic irradiation of primary prostate cancer at 5x9 Gy with a method of urethral sparing.

OBJECTIVE: The most commonly used dose for prostate cancer stereotactic body radiotherapy (SBRT) is 5 × 7.25 Gy. The aim of this study was to evaluate the dosimetric feasibility of a 5 × 9 Gy SBRT regimen while still limiting the dose to the urethra to 5 × 7.25 Gy. This dosimetric study is part of the groundwork for a future Phase III randomized trial. METHODS: The prostate, the urethra and the tumors were delineated on 20 dosimetric CT-scans with MRI-registration. The planning target volume (PTVp) was defined as a 5 mm expansion (3 mm posteriorly) of the prostate. The planning at risk volume (PRVu) was defined as a 2 mm expansion of the urethra. The tumors were delineated on the MRI (GTVt) and a 3 mm-margin was added to create a tumoral planning target volume (PTVt). IMRT plans were optimized to deliver 5 × 9 Gy to the PTVp, limiting the dose to the PRVu to 5 × 7.25 Gy. Results are presented using average (range) values. RESULTS: PTVp doses were D98% = 36.2 Gy (35.6-36.8), D2% = 46.9 Gy (46.5-47.5) and mean dose = 44.1 Gy (43.8-44.5). The dose to the PRVu was within tolerance limits for all 20 patients: V34.4Gy = 99.8% (99.2-100) and D5% = 38.7 Gy (38.6-38.8). Dose coverage of PTV-PRVu was D95% = 40.6 Gy (40.5-40.9), D5% = 46.6 Gy (46.2-47.2) and mean dose = 44.6 Gy (44.3-44.9). Dose to the PTVt reached 44.6 Gy (41.2-45.9). Doses to the OAR were respected, except V36Gy ≤1 cc for the rectum. CONCLUSION: A SBRT dose-escalation to 5 × 9 Gy on the prostate while sparing the urethra + 2 mm at 36.25 Gy is feasible without compromising dose coverage to the tumor. This radiation regimen will be used for a Phase-III trial. ADVANCES IN KNOWLEDGE: In prostate SBRT, dose optimization on the urethra is feasible and could decrease urinary toxicities.

Intensity-modulated radiation therapy with simultaneous integrated boost for locally advanced breast cancer: a prospective study on toxicity and quality of life.

Radiotherapy after breast conserving surgery and mastectomy with node positive disease has been shown to reduce risk of recurrence and mortality in the treatment of breast cancer. Intensity-modulated radiation therapy (IMRT) after conservative surgery offers several advantages over conventional RT including improved acute and late toxicity and quality of life (QoL). We undertook this study to prospectively evaluate acute (≤90 days after last dose of radiotherapy) and long-term (>90 days) cutaneous, esophageal, and fibrosis toxicity and QoL in breast cancer patients treated by adjuvant IMRT after breast surgery. We included patients with complex volumes for which 3D RT does not allow a good coverage of target volumes and sparing organs at risk. We report here an interim analysis with a median follow-up of 13.1 months (range, 6.5-25.9 months). Most of the acute toxicity was cutaneous (95.9%) and oesophageal (59.6%), and mostly grade 1 and 2. Medium-term cutaneous toxicity rate was 25.6%, and mostly grade 1. Medium-term esophageal toxicity was rare (1.8%). In this series acute oesophageal toxicity was found to be associated with dosimetric factors. QoL was well preserved throughout the study, and aesthetic outcomes were good. Based on these data, tomotherapy may be a favorable alternative to other techniques in patients needing a complex irradiation of the breast and lymph node volumes.

Prostate brachytherapy under hypnosedation: A prospective evaluation.

PURPOSE: Hypnosedation (HS) for brachytherapy has been proposed in patients with prostate cancer and has been evaluated. MATERIALS AND METHODS: 79 patients were treated with brachytherapy under HS. The Visual Analog Scale questionnaire was used to assess comfort and anxiety and the lowest, mean, and highest level of pain. Data for 79 patients who underwent general anesthesia (GA) and 37 patients who underwent spinal anesthesia (SA) treated at the same period were compared with HS group in terms of medication and treatment duration. RESULTS: 11 patients (13.9%) requested a GA, because they did not reach the hypnotic level. For the remaining 68 patients, the mean pain and comfort scores evaluated just after the intervention were 3.1 and 7.4, respectively. At 8 weeks, the scores were 2.8 and 7.5, respectively. 66 patients (97%) would choose this approach again and recommend it to other patients. The patients in the HS group received significant less medications than in the GA (remifentanil, propofol, kétamine, phenylephrine, ephedrine…) or SA (sufentanil, midazolam, morphine, bupivacaine…) groups with mean values of 3.1 vs. 7.9 vs. 5.6 (p < 0.0001), respectively. HS increased the mean time of surgery room occupation by 12 min vs. GA and by 20 min vs. SA. However, the recovery room occupation is avoided with HS (GA = 61 min and SA = 67 min) and a shorter duration of a need for a urinary catheter was noted. CONCLUSIONS: HS is a feasible and comfortable method of anesthesia and a good alternative to GA and SA for patients undergoing prostate brachytherapy, with reduced treatment duration and number of medications.

Larynx preservation: what is the standard treatment?

Locally advanced laryngeal and hypo-pharyngeal cancers have a rather poor prognosis. Up until the early 1990s, standard treatment was total laryngectomy, with dramatic functional and social outcome. The introduction of cisplatin based chemotherapy made concurrent chemo-radiotherapy (CCRT) the standard treatment for selected patients, fit for an organ preservation strategy. Over two decades of improvement in nonsurgical management of locally advanced laryngeal cancer is reviewed, including the most recent improvements with the introduction of taxanes and anti-EGFR targeted therapy.

Palliative chemotherapy does not improve survival in metastatic esophageal cancer.

BACKGROUND: The role of chemotherapy in metastatic esophageal carcinoma (MEC) remains a matter of debate. The aim of this retrospective study was to analyze the survival impact of chemotherapy after stratification for prognostic factors. METHODS: Consecutive patients with MEC (1995 to 2008) were randomly assigned to a development (n = 171) and a validation cohort (n = 113). We had first identified prognostic factors using the Kaplan-Meier and Cox methods in the development cohort and then validated them in the validation cohort. Then, we analyzed the impact of chemotherapy after stratification for these prognostic factors. The majority of patients had squamous cell carcinoma (80%). RESULTS: The Cox model has retained 2 prognostic factors only: associated cancers (hazard ratio = 2.77, range 1.39-5.54, p = 0.004) and grade 3-4 dysphagia (hazard ratio = 1.44, range 1.08-2.14, p = 0.007). Median survival was 10.9 in patients with 0 (n = 77), 6.2 in those with 1 (n = 65) and 1.8 months in those with 2 prognostic factors (n = 11/171; p = 0.025). The median survival times of the patients with 0, 1 and 2 prognostic factors were 13 versus 9 months (nonsignificant, NS), 6 versus 5 months (NS) and 5 versus 1.3 months (NS) in patients with and without chemotherapy, respectively. CONCLUSION: Our data suggest that chemotherapy has no significant effect on survival for unselected MEC patients, regardless of the prognostic factors we identified.