Efficiency and Accuracy Evaluation of Multiple Diffusion-Weighted MRI Techniques Across Different Scanners.

BACKGROUND: The choice between different diffusion-weighted imaging (DWI) techniques is difficult as each comes with tradeoffs for efficient clinical routine imaging and apparent diffusion coefficient (ADC) accuracy. PURPOSE: To quantify signal-to-noise-ratio (SNR) efficiency, ADC accuracy, artifacts, and distortions for different DWI acquisition techniques, coils, and scanners. STUDY TYPE: Phantom, in vivo intraindividual biomarker accuracy between DWI techniques and independent ratings. POPULATION/PHANTOMS: NIST diffusion phantom. 51 Patients: 40 with prostate cancer and 11 with head-and-neck cancer at 1.5 T FIELD STRENGTH/SEQUENCE: Echo planar imaging (EPI): 1.5 T and 3 T Siemens; 3 T Philips. Distortion-reducing: RESOLVE (1.5 and 3 T Siemens); Turbo Spin Echo (TSE)-SPLICE (3 T Philips). Small field-of-view (FOV): ZoomitPro (1.5 T Siemens); IRIS (3 T Philips). Head-and-neck and flexible coils. ASSESSMENT: SNR Efficiency, geometrical distortions, and susceptibility artifacts were quantified for different b-values in a phantom. ADC accuracy/agreement was quantified in phantom and for 51 patients. In vivo image quality was independently rated by four experts. STATISTICAL TESTS: QIBA methodology for accuracy: trueness, repeatability, reproducibility, Bland-Altman 95% Limits-of-Agreement (LOA) for ADC. Wilcoxon Signed-Rank and student tests on P < 0.05 level. RESULTS: The ZoomitPro small FOV sequence improved b-image efficiency by 8%-14%, reduced artifacts and observer scoring for most raters at the cost of smaller FOV compared to EPI. The TSE-SPLICE technique reduced artifacts almost completely at a 24% efficiency cost compared to EPI for b-values ≤500 sec/mm2 . Phantom ADC 95% LOA trueness were within ±0.03 × 10-3 mm2 /sec except for small FOV IRIS. The in vivo ADC agreement between techniques, however, resulted in 95% LOAs in the order of ±0.3 × 10-3 mm2 /sec with up to 0.2 × 10-3 mm2 /sec of bias. DATA CONCLUSION: ZoomitPro for Siemens and TSE SPLICE for Philips resulted in a trade-off between efficiency and artifacts. Phantom ADC quality control largely underestimated in vivo accuracy: significant ADC bias and variability was found between techniques in vivo. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

Sequential combination of Sonic Hedgehog inhibitors followed by consolidation radiotherapy in locally advanced basal cell carcinoma.

BACKGROUND: Sonic Hedgehog inhibitors (SHHis) are an effective treatment in locally advanced basal cell carcinoma (laBCC), but the use of these drugs is limited by adverse events and relapse at discontinuation in around half of patients. A few cases of patients treated concomitantly by radiotherapy (RT) and SHHis have been reported in the literature, suggesting that the combination results in an improved overall response. Maintaining complete response after stopping treatment is a concern, especially since resuming treatment in the case of relapse does not guarantee a new therapeutic response. The optimal combination and sequence of treatment to improve local control of laBCCs are not yet defined. OBJECTIVE: We hypothesized that consolidation RT after complete response to SHHis could reduce the risk of relapse at discontinuation. METHODS: We present a case series of patients with laBCCs who achieved complete response (CR) after SHHi treatment and were treated with consolidation RT. Patients were evaluated by a skin cancer board. The closure RT technique and dosage were refined by a radiotherapist. RESULTS: Eleven patients were included. SHHis were prescribed for 5 months (range 4-11). Consolidation RT was performed after CR to SHHis and discontinuation. RT was delivered at a median dose of 45 Gy (range 40.5-66) in 10 fractions (range 9-33). With a median follow-up of 23 months, all patients maintained complete clinical response. This strategy was well tolerated with no grade 3 adverse events. CONCLUSION: SHHi treatment followed by RT consolidation after drug discontinuation seems effective and safe. Further studies are needed to develop a precise strategy for the management of laBCCs.

Association of Radiochemotherapy to Immunotherapy in unresectable locally advanced Oesophageal carciNoma-randomized phase 2 trial ARION UCGI 33/PRODIGE 67: the study protocol.

BACKGROUND: In case of locally advanced and/or non-metastatic unresectable esophageal cancer, definitive chemoradiotherapy (CRT) delivering 50 Gy in 25 daily fractions in combination with platinum-based regimen remains the standard of care resulting in a 2-year disease-free survival of 25% which deserves to be associated with new systemic strategies. In recent years, several immune checkpoint inhibitors (anti-PD1/anti-PD-L1, anti-Program-Death 1/anti-Program-Death ligand 1) have been approved for the treatment of various solid malignancies including metastatic esophageal cancer. As such, we hypothesized that the addition of an anti-PD-L1 to CRT would provide clinical benefit for patients with locally advanced oesophageal cancer. To assess the efficacy of the anti-PD-L1 durvalumab in combination with CRT and then as maintenance therapy we designed the randomized phase II ARION (Association of Radiochemotherapy with Immunotherapy in unresectable Oesophageal carciNoma- UCGI 33/PRODIGE 67). METHODS: ARION is a multicenter, open-label, randomized, comparative phase II trial. Patients are randomly assigned in a 1:1 ratio in each arm with a stratification according to tumor stage, histology and centre. Experimental arm relies on CRT with 50 Gy in 25 daily fractions in combination with FOLFOX regimen administrated during and after radiotherapy every two weeks for a total of 6 cycles and durvalumab starting with CRT for a total of 12 infusions. Standard arm is CRT alone. Use of Intensity Modulated radiotherapy is mandatory. The primary endpoint is to increase progression-free survival at 12 months from 50 to 68% (HR = 0.55) (power 90%; one-sided alpha-risk, 10%). Progression will be defined with central external review of imaging. ANCILLARY STUDIES ARE PLANNED: PD-L1 Combined Positivity Score on carcinoma cells and stromal immune cells of diagnostic biopsy specimen will be correlated to disease free survival. The study of gut microbiota will aim to determine if baseline intestinal bacteria correlates with tumor response. Proteomic analysis on blood samples will compare long-term responder after CRT with durvalumab to non-responder to identify biomarkers. CONCLUSION: Results of the present study will be of great importance to evaluate the impact of immunotherapy in combination with CRT and decipher immune response in this unmet need clinical situation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT: 03777813.Trial registration date: 5th December 2018.

Stereotactic body radiotherapy for intramedullary metastases: a retrospective series at the Oscar Lambret center and a systematic review.

BACKGROUND: Intramedullary metastasis (IMM) is a rare disease with poor prognosis. The incidence of IMMs has increased, which has been linked to improved systemic treatment in many cancers. Surgery and/or radiotherapy are the most commonly used treatments; only small-sample retrospective studies and case reports on stereotactic body radiotherapy (SBRT) have reported acceptable results in terms of local control and clinical improvement, with no reported toxicity. Thus, we performed this monocentric retrospective study on five cases treated with SBRT for IMMs, which we supplemented with a systematic review of the literature. METHODS: We included all patients treated for IMM with SBRT. The target tumor volume, progression-free survival, prescription patterns in SBRT, survival without neurological deficit, neurological functional improvement after treatment, and overall survival were determined. RESULTS: Five patients treated with a median dose of 30 Gy in a median number of fractions of 5 (prescribed at a median isodose of 86%) included. The median follow-up duration was 23 months. Two patients showed clinical improvement. Three patients remained stable. Radiologically, 25% of patients had complete response and 50% had stable disease. No significant treatment-related toxicity was observed. CONCLUSION: SBRT appears to be a safe, effective, and rapid treatment option for palliative patients.

Evaluation of an ultrasound bladder scanner in supine and standing position.

PURPOSE: This study examined the performance of a bladder volume measuring device, the BladderScan (BS) BVI9400. The use of the BS offers the possibility of assessing the bladder volume before positioning the patient and performing the daily image-guided radiotherapy procedure. Patients often cannot lie down before entering the treatment vault. Therefore, the BS was also assessed in a standing position. METHODS: The repeatability precision was first evaluated, which is the variability of immediate repeated measures of the BS with same operator and subject. This was followed by the reproducibility precision of the BS in which the operator and subjects differ. Finally, the trueness was evaluated in terms of fixed and proportional bias of the results by applying weighted least-squares fitting. Note that 53 and 85 patient measurements were carried out in supine and standing position, respectively, each consisting of three repeated BS measurements. These were compared with the computed tomography (CT)-delineated bladder volume. RESULTS: Repeatability was dependent on measurement value (heteroscedasticity) with σrepeatability (BS) = ±15 cm3  ± 10%. However, the total agreement between BS and CT was low with the 95% limits of agreement (LOAs) exceeding ±200 cm3 due to poor patient reproducibility and presence of fixed and proportional bias. Only in the best case of male patients in the supine position, three BS measurements, and correction for the fixed and proportional bias, 95% LOAs of [-147, +114] cm3 were obtained between CT and BS. CONCLUSION: The agreement of the BVI9400 BS with CT was found to be too low for radiotherapy applications.

Outcomes of pre-operative brachytherapy followed by hysterectomy for early cervical cancer.

OBJECTIVE: The standard of care for early cervical cancer is radical hysterectomy; however, consideration of pre-operative brachytherapy has been explored. We report our experience using pre-operative brachytherapy plus Wertheim-type hysterectomy to treat early stage cervical cancer. METHODS: This single-center study evaluated consecutive patients with histologically proven node-negative early stage cervical cancer (International Federation of Gynecology and Obstetrics 2009 stage IB1-IIB) that was treated using pre-operative brachytherapy and hysterectomy. Pre-brachytherapy staging was performed using magnetic resonance imaging (MRI) and pelvic lymph node assessment was performed using lymphadenectomy. The tumor and cervical tissues were treated using brachytherapy (total dose 60 Gy) followed by Wertheim-type hysterectomy. The study included patients from January 2000 to December 2013. RESULTS: A total of 80 patients completed a median follow-up of 6.7 years (range 5.4-8.5). The surgical specimens revealed a pathological complete response for 61 patients (76%). Patients with incomplete responses generally had less than 1 cm residual tumor at the cervix, and only one patient had lymphovascular space involvement. The estimated 5-year rates were 88% for overall survival (95% CI 78% to 94%) and 82% for disease-free survival (95% CI 71% to 89%). Toxicities were generally mild-to-moderate, including 26 cases (33%) of grade 2 late toxicity and 10 cases (13%) of grade 3 late toxicity. Univariate analyses revealed that poor disease-free survival was associated with overweight status (≥25 kg/m2, HR 3.05, 95% CI 1.20 to 7.76, p=0.019) and MRI tumor size >3 cm (HR 3.05, 95% CI 1.23 to 7.51, p=0.016). CONCLUSIONS: Pre-operative brachytherapy followed by Wertheim-type hysterectomy may be safe and effective for early stage cervical cancer, although poorer outcomes were associated with overweight status and MRI tumor size >3 cm.

Combination of High Dose Hypofractionated Radiotherapy with Anti-PD1 Single Dose Immunotherapy Leads to a Th1 Immune Activation Resulting in a Complete Clinical Response in a Melanoma Patient.

The development of immunotherapy has recently modified the anti-tumor therapeutic arsenal; particularly, immune checkpoint inhibitors have led to a significant increase in overall survival. The current challenge is now to select good responder patients by identifying early biomarkers to propose therapeutic combinations that potentiate the efficacy of the therapy. Here we report the case of a 60-year-old man with superficial melanoma treated with high-dose hypo fractionated radiotherapy (H-SRT) combined with a single dose of anti-PD1 immunotherapy (Nivolumab) for a metastatic lymph node recurrence due to cancer progression. In this study, we present the results obtained regarding the activation of the Th1 immune response after H-SRT treatment followed by anti PD-1 therapeutic protocol. These results were correlated with clinical data to identify potential immunological biomarkers of treatment efficacy. This exceptional case report shows that a combination of H-SRT with a single dose of anti-PD1 immunotherapy may allow a better activation of the immune response in favor of a complete clinical response.

Esophageal Adenocarcinoma: Impact of a Large Hiatal Hernia on Outcomes After Surgery.

OBJECTIVE: To evaluate complete tumor resection rate (primary objective), 30-day postoperative outcomes, and survival (secondary objectives) in patients with a hiatal hernia (HH) ≥5 cm (HH group) compared with those who did not have a HH or presented with a HH <5 cm (control group). BACKGROUND: HH is a risk factor for esophageal and junctional adenocarcinoma (EGJA). Its impact on the outcomes after EGJA surgery is unknown. METHODS: Among 367 patients who underwent surgery for EGJA, a HH was searched for on computerized tomography scan and barium swallow, with comparison between the HH (n = 42) and control (n = 325) groups. RESULTS: In the HH group, EGJAs exhibited higher rates of incomplete resection (50.0% vs 4.0%; P < 0.001), of pN3 stages (28.5% vs 10.1%; P = 0.002), and lower median survival (20.9 vs 41.0 mos; P = 0.001). After adjustment, a HH ≥5 cm was a predictor of incomplete resection (odds ratio 21.0, 95% confidence interval 9.4-46.8, P < 0.001) and a poor prognostic factor (hazard ratio 1.6, 95% confidence interval 1.1-2.5, P = 0.025). In the HH group, 30-day mortality was significantly higher in patients who received neoadjuvant radiotherapy (20.0% vs 0%; P = 0.040), which was related to greater cardiac and pulmonary toxicity. CONCLUSIONS: For the first time, we showed that a HH ≥5 cm is associated with a poor prognosis in patients who had surgery for EGJA, linked to greater incomplete resection and lymph node involvement. Neoadjuvant radiotherapy was associated with a significant toxicity in patients with a HH ≥5 cm.

Preoperative chemoradiation with paclitaxel-carboplatin or with fluorouracil-oxaliplatin-folinic acid (FOLFOX) for resectable esophageal and junctional cancer: the PROTECT-1402, randomized phase 2 trial.

BACKGROUND: Often curative treatment for locally advanced resectable esophageal or gastro-esophageal junctional cancer consists of concurrent neoadjuvant radiotherapy and chemotherapy followed by surgery. Currently, one of the most commonly used chemotherapy regimens in this setting is a combination of a fluoropyrimidin and of a platinum analogue. Due to the promising results of the recent CROSS trial, another regimen combining paclitaxel and carboplatin is also widely used by European and American centers. No clinical study has shown the superiority of one treatment over the other. The objective of this Phase II study is to clarify clinical practice by comparing these two chemotherapy treatments. Our aim is to evaluate, in operable esophageal and gastro-esophageal junctional cancer, the complete resection rate and severe postoperative morbidity rate associated with these two neoadjuvant chemotherapeutic regimens (carboplatin-paclitaxel or fluorouracil-oxaliplatin-folinic acid) when each is combined with the radiation regime utilized in the CROSS trial. METHODS/DESIGN: PROTECT is a prospective, randomized, multicenter, open arms, phase II trial. Eligible patients will have a histologically confirmed adenocarcinoma or squamous cell carcinoma and be treated with neoadjuvant radiochemotherapy followed by surgery for stage IIB or stage III resectable esophageal cancer. A total of 106 patients will be randomized to receive either 3 cycles of FOLFOX combined to concurrent radiotherapy (41.4 Grays) or carboplatin and paclitaxel with the same radiation regimen, using a 1:1 allocation ratio. DISCUSSION: This ongoing trial offers the unique opportunity to compare two standards of chemotherapy delivered with a common regimen of preoperative radiation, in the setting of operable locally advanced esophageal or gastro-esophageal junctional tumors. TRIAL REGISTRATION: NCT02359968 (ClinicalTrials.gov) (registration date: 9 FEB 2015), EudraCT: 2014-000649-62 (registration date: 10 FEB 2014).

Stereotactic reirradiation in the treatment of head and neck cancers: A retrospective study on the long-term experience of the Oscar Lambret Center.

BACKGROUND AND PURPOSE: Stereotactic radiotherapy potentially treats unresectable recurrences of previously irradiated head and neck (H&N) cancer. This study aimed to assess its efficacy and safety and evaluate prognostic factors. MATERIALS AND METHODS: We conducted a large retrospective series that included 110 patients who had undergone 36-Gy, six-fraction stereotactic reirradiation (CyberKnife®) for recurrent/secondary H&N cancer between 2007 and 2020 at the Oscar Lambret Center. Patient characteristics and toxicities were assessed. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. RESULTS: Median follow-up time was 106.3 months. The 2-year OS rate was 43.8 % (95 % confidence interval, 95 % CI, 34.3-52.9) and the median survival was 20.8 months (95 % CI, 16.5-26.3). The cumulative 2-year local-recurrence, regional-recurrence, and distant-metastasis rates were 52.2 % (95 % CI, 42.4-61.1 %), 12.8 % (95 % CI, 7.4-19.8 %), and 11 % (95 % CI, 6.0-17.6 %), respectively. 73 patients received concomitant cetuximab, and it was not significantly beneficial (HR = 1.34; 95 % CI, 0.80-2.26; p = 0.26). The cumulative incidences of grade ≥ 2 late toxicity was 42 % (CI95%: 33-51) at 24 months. Two grade 4 bleedings and no treatment-related deaths were reported. CONCLUSION: In a large retrospective series of SBRT reirradiation for recurrent or second primary H&N cancers, we observed a median OS of 20.8 months, with a cumulative incidence of grade ≥ 2 late toxicity of 42 % at 24 months. Such a treatment is feasible. However, local recurrence rates remain non-negligible, warranting further research. Radiosensitizer use is currently under study. Therefore, establishing a balance between therapeutic modifications and toxicity is essential.

Stereotactic body radiotherapy as a viable treatment on extracranial oligometastases in melanoma patients: a retrospective multicentric study.

Introduction: Stereotactic radiotherapy (SBRT) potentially has a role in the management of oligometastatic melanoma. However, literature with data specific to this management is very limited. The objectives of this study were to evaluate the time to local control (LC) of extra-cranial melanoma metastases after SBRT treatment and to help establish if SBRT is a useful therapy for oligometastatic melanoma. Methods: A retrospective study was conducted with data collected from two referral centers in France between 2007 and 2020. The oligometastatic status of patients was reported based on the latest recommendations with a maximum of three lesions prior to treatment. Results: A total of 69 patients receiving SBRT for 88 oligometastatic melanoma metastases were included. The median follow-up time was 42.6 months. Most patients were treated for metachronous oligometastatic lesions. Occurrence of oligoprogression, oligorecurrence, and oligopersistence was reported in 42.0%, 39.1%, and 17.4% of cases, respectively. Treated lesions were mostly pulmonary (40.6%), followed by lymph node (34.8%) and hepatic sites (24.6%). Progression-free survival at 1, 2, and 3 years were 47.0% (35-59), 27.0% (16-39), and 25.0% (15.0-37.0), respectively. Time to LC rates at 1, 2, and 3 years were 94.2% (87.0-98.1), 90.3% (81.3-96.1), and 90.3% (81.3-96.1), respectively. Overall survival at 1, 2, and 3 years were 87% (76.0-93.0), 74.0% (76.0-93.0), and 61.0% (47.0-73.0), respectively. Only 17.4% of patients experienced acute, grade 1 or grade 2 toxicities with no reports of grade 3 or higher toxicities. Conclusion: SBRT demonstrated efficacy in managing melanoma patients with extracranial oligometastases and showed an overall low toxicity profile. Future randomized studies are needed to establish the role of SBRT in therapeutic approaches for patients with oligometastatic melanoma.

Intermediate-risk endometrial cancer treated with adjuvant brachytherapy using single dosimetric planning: long-term outcome and toxicity assessment.

OBJECTIVE: Brachytherapy of the vaginal dome is the recommended adjuvant treatment for intermediate-risk endometrial cancer. This study assessed the results of dosimetric planning of high-dose-rate brachytherapy exclusively in the first treatment session. STUDY DESIGN: This retrospective study included all patients who underwent hysterectomy for endometrial cancer followed by adjuvant brachytherapy of the vaginal dome between 2012 and 2015. Local recurrence rates, overall survival (OS) rates, recurrence-free survival (RFS) rates, and related acute and late toxicity rates were evaluated. RESULTS: This analysis included 250 patients, of whom 208 were considered to be at high-intermediate risk of disease recurrence. After a median follow-up of 56 months, the cumulative incidence of local recurrence was 4.8% at 3 years [95% confidence interval (CI) 2.8-8.3] and 7.8% at 5 years (95% CI 4.8-12.6). The 5-year OS rate was 86.2% (95% CI 80.6-90.3), and the 5-year RFS rate was 77.5% (95% CI 71.1-82.7). Acute toxicity occurred in 20 (8%) patients, of which two patients had grade ≥3 toxicity. Only one patient (0.4%) presented with late grade ≥3 toxicity. CONCLUSION: These findings confirm the tolerability of this brachytherapy approach, indicating minimal cases of late grade ≥3 toxicity, associated with a good 5-year OS rate. With the advent of molecular prognostic factors, the current focus revolves around discerning those individuals who gain the greatest benefit from adjuvant therapy, and tailoring treatment more effectively.

Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma: Meta-Analysis and International Stereotactic Radiosurgery Society Practice Guidelines.

This systematic review and meta-analysis reports on outcomes and hepatic toxicity rates after stereotactic body radiation therapy (SBRT) for liver-confined hepatocellular carcinoma (HCC) and presents consensus guidelines regarding appropriate patient management. Using the Preferred Reporting Items for Systemic Review and Meta-Analyses guidelines, a systematic review was performed from articles reporting outcomes at ≥5 years published before October 2022 from the Embase, MEDLINE, Cochrane, and Scopus databases with the following search terms: ("stereotactic body radiotherapy" OR "SBRT" OR "SABR" OR "stereotactic ablative radiotherapy") AND ("hepatocellular carcinoma" OR "HCC"). An aggregated data meta-analysis was conducted to assess overall survival (OS) and local control (LC) using weighted random effects models. In addition, individual patient data analyses incorporating data from 6 institutions were conducted as their own subgroup analyses. Seventeen observational studies, comprising 1889 patients with HCC treated with ≤9 SBRT fractions, between 2003 and 2019, were included in the aggregated data meta-analysis. The 3- and 5-year OS rates after SBRT were 57% (95% confidence interval [CI], 47%-66%) and 40% (95% CI, 29%-51%), respectively. The 3- and 5-year LC rates after SBRT were 84% (95% CI, 77%-90%) and 82% (95% CI, 74%-88%), respectively. Tumor size was the only prognostic factor for LC. Tumor size and region were significantly associated with OS. Five-year LC and OS rates of 79% (95% CI, 0.74-0.84) and 25% (95% CI, 0.20-0.30), respectively, were observed in the individual patient data analyses. Factors prognostic for improved OS were tumor size <3 cm, Eastern region, Child-Pugh score ≤B7, and the Barcelona Clinic Liver Cancer stage of 0 and A. The incidence of severe hepatic toxicity varied according to the criteria applied. SBRT is an effective treatment modality for patients with HCC with mature follow-up. Clinical practice guidelines were developed on behalf of the International Stereotactic Radiosurgery Society (ISRS).

Ineffectiveness of ¹8F-fluorodeoxyglucose positron emission tomography in the evaluation of tumor response after completion of neoadjuvant chemoradiation in esophageal cancer.

OBJECTIVE: To evaluate the role of ¹8F-fluorodeoxyglucose-positron emission tomography (FDG-PET) in the assessment of tumor response after the completion of neoadjuvant chemoradiation (CRT) in patients with locally advanced resectable esophageal cancer. BACKGROUND: After primary CRT, a noninvasive evaluation of the tumor response could help in the treatment decision to identify patients who may benefit from surgery. Whether FDG-PET provides clinically relevant information remains questionable. METHODS: Operable patients with locally advanced esophageal cancer (clinically staged T3 N0-1 M0) were enrolled in this prospective study. The complete treatment plan included neoadjuvant CRT (cisplatin + 5-fluorouracil/45 Gy) followed 6 to 8 weeks later by a transthoracic en bloc esophagectomy. Morphological evaluation combined with FDG-PET was performed 2 weeks before the start of CRT and 4 to 6 weeks after the completion of CRT. Intratumoral pre- and posttreatment FDG-standardized uptake values (SUV1, SUV2, percentage change) were assessed. These variables were correlated with pathological and morphologic responses and survival. Investigators were blinded to the FDG-PET results unless they revealed metastatic disease. RESULTS: Of 60 total patients, 46 underwent the complete treatment plan (median age: 60.1 years; adenocarcinoma: 25 patients; squamous cell cancer: 21 patients). A major pathological response occurred in 45.7% of patients and was associated with a favorable outcome (P = 0.057). Neoadjuvant CRT led to a significant reduction in intratumoral FDG-uptake (P < 0.001). No significant association was seen between a pathological response (either complete or major) and the FDG-PET results (P > 0.280). The SUV2 value was correlated with a morphological response and the possibility to perform an R0 resection (P < 0.018; receiver operating characteristic curve analysis: SUV2 threshold = 5.5). No significant association was found between metabolic imaging and recurrence or survival. CONCLUSIONS: FDG-PET does not effectively correlate with pathological response and long-term survival in patients with locally advanced esophageal cancer undergoing neoadjuvant CRT followed by surgery. (Registered on the www.e-cancer RECF0350.).

Is there a role for surgery for patients with a complete clinical response after chemoradiation for esophageal cancer? An intention-to-treat case-control study.

OBJECTIVE: To compare the outcomes of a strategy of surveillance versus surgical resection in patients with esophageal cancer (EC) experiencing complete clinical response (cCR) after chemoradiation (CRT). BACKGROUND: In EC, it remains unclear whether a strategy of surveillance or esophagectomy is appropriate after cCR to CRT. METHODS: From 1995 to 2009, 222 operable patients had a cCR based on the results of a computed tomographic scan, endoscopy with biopsies and, when performed, a positron emission tomographic scan. Through an intention-to-treat case-control study, 59 patients treated with CRT and surveillance (group Surv) were matched 1:2 with 118 patients treated by CRT followed by surgery (group Surg), according to age, gender, tumor location and stage, histology, American Society of Anesthesiologists score, and nutritional status. RESULTS: The 2 groups were comparable according to the matched variables (P > 0.276). In group Surg, the postoperative mortality rate was 4.2% with evidence of residual tumor in 34.6% of specimens. In group Surv, 2 salvage esophagectomies were performed. Despite the higher dose of radiotherapy received in group Surv (50 vs 45 Gys, P = 0.003), median survival was lower (31 vs 83 months, P = 0.001), with disease recurrence that was more frequent (50.8% vs 32.7%, P = 0.021), occurred earlier (7.8 vs 19.0 months, P = 0.002) and more often locoregional (46.7% vs 16.2%, P = 0.007) in nature. Surgical resection was independently associated with less recurrence [odds ratio = 0.4, 95% confidence interval (CI): 0.2-0.8, P = 0.006] and better survival (hazard ratio = 0.5, 95% CI: 0.3-0.8, P = 0.006). CONCLUSIONS: Survival of EC patients with a cCR after CRT is better after surgery compared to simply surveillance. In patients of low operative risk and operable disease, surgery should be considered to improve control of locoregional disease and to overcome the inherent limitations of clinical response assessment.

Clinical complete responders to definite chemoradiation or radiation therapy for oesophageal cancer: predictors of outcome.

BACKGROUND: To identify predictors of long-term outcome for patients with clinical complete response (cCR) after definite chemoradiotherapy (CRT) or radiation therapy (RT) for oesophageal cancer (EC). METHODS: In this retrospective study, we reviewed the files of all patients from our institution that underwent definitive RCT or RT for EC, from January 1998 to December 2003. Among 402 consecutive patients with EC, 110 cCR responses were observed, i.e. without evidence of tumour on morphological examination of the biopsy specimens, 8 to 10 weeks after radiation. Baseline patient and tumour characteristics were as follows: male = 98/110, median age = 60, squamous histology = 103/110, tumour site (upper/middle/lower third) = 41/50/19, weight loss none/<10%/≥10% = 36/45/29, dysphagia grade 1/2/≥3 = 30/14/66. Patients were staged according to endosonography and/or computed tomography. There were 9 stage I, 31 stage IIA, 15 stage IIB, 41 stage III, 6 stage IV. Post treatment nutritional characteristics were as follows: weight loss during treatment none/<10% ≥ 10% = 35/38/37, remaining dysphagia grade 1/2/≥3 = 54/24/32. Univariate and multivariate analyses were performed using log-rank and Cox proportional hazards models, and survival curves were estimated using the Kaplan-Meier method. RESULTS: During follow up (median: 6 [0.4-9.8] years), 16 patients had salvage surgery. Median OS was 2.5 years, and 5-year OS was 33.5%. Histological type, stage, age, gender, and treatment characteristics had no significant impact on outcome. The risk of death was increased two-fold for patients with grade ≥ 3 dysphagia after treatment (HR = 1.9 [1.2-3.1], p = 0.007). Weight loss ≥10% during treatment also negatively affected outcome (HR = 1.8 [1.0-3.2], p = 0.040). CONCLUSION: One EC patient among 3 with cCR after definite CRT/RT is still alive at 5 years. Variables related to reduced OS were: remaining significant dysphagia after treatment and weight loss ≥10% during treatment.

Effects of Proton Pump Inhibitors Intake During Chemoradiotherapy for Rectal Cancer: a Retrospective Cohort Study.

PURPOSE: Proton pump inhibitors (PPIs) are one of the most widely used drugs worldwide and are involved in several drug interactions. Recently, several studies have suggested that PPIs may interfere with the efficacy of capecitabine. This study primarily aimed to investigate the effects of PPI intake on the pathologic response rate of patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy with capecitabine. METHOD: A retrospective study was conducted at a French Comprehensive Cancer Center. Patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by surgery were included in the study. Demographic parameters, treatment characteristics, survival data, and PPI intake data were collected. Frequencies and percentages were reported for categorical variables and medians and interquartile ranges for continuous variables. Distribution of variables was compared according to PPI treatment using the chi-square test or Fisher's exact test for categorical data and nonparametric Wilcoxon tests for continuous variables. Survival data were estimated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: In total, 215 patients were included, of whom 135 (62.8%) were men. The PPI intake frequency was 16.1%. The rate of complete pathological response was not significantly lower in patients on PPIs than in those not on PPIs (8.7% vs. 19%, p = 0.36). PPI intake was not associated with a statistically significant decrease in recurrence-free survival (hazard ratio [HR] = 1.26, 95% confidence interval [CI] 0.61-2.60, p = 0.54) or overall survival (HR = 0.95, 95% CI 0.33-2.76, p = 0.93). CONCLUSION: No significant association was observed between PPI co-medication and complete pathological response or survival in patients treated for locally advanced rectal cancer. However, the safety of PPIs could not be confirmed. Further ancillary studies of prospective clinical trials or studies using the Health Data Hub are necessary to explore the effects of PPIs on rectal cancer more accurately.

An Effective Primary Treatment Using Radiotherapy in Patients with Eyelid Merkel Cell Carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare type of neuroendocrine tumor. Palpebral localization represents 2.5% of MCCs. Surgery is not always possible due to the localization or comorbidities of elderly patients. We hypothesized that radiotherapy (RT) alone could be a curative treatment in patients contraindicated for oncological surgery. METHODS: We performed a retrospective monocentric study of patients with localized eyelid MCC treated with curative intent using curative radiotherapy. RESULTS: Overall, 11 patients with histologically confirmed eyelid MCC were treated with curative radiotherapy. The median age was 77 years old (range: 53-94). Curative RT was decided mainly due to difficult localization and significant co-morbidities. The median lesion dose was 57 Gy (range: 47-70). Most patients had adjuvant lymph nodes irradiation with a median dose of 50 Gy (n = 9; 82%). The median follow-up was 62 months (6-152 months). None of the seven deaths were MCC-related. None of our patients relapsed during follow-up. Side effects related to radiotherapy were mild (no grade ≥ 2) and rare (n = 3, 21%). CONCLUSION: Our data suggest that curative radiotherapy is an effective and safe treatment for Merkel cell carcinoma of the eyelid and periocular region. Radiotherapy alone allows limiting the aesthetic and functional sequelae in elderly and comorbid patients who are contraindicated for oncological surgery.

Evaluation of surface image guidance and Deep inspiration Breath Hold technique for breast treatments with Halcyon.

PURPOSE: To evaluate the accuracy/agreement of a three-camera Catalyst Surface Guided Radiation Therapy (SGRT) system on a closed-gantry Halcyon for Free-Breathing (FB) and Deep Inspiration Breath Hold (DIBH) breast-only treatments. METHODS: The SGRT positioning agreement with Halcyon couch and cone-beam computed tomography (CBCT) was evaluated on phantom and by evaluation of 2401 FB and 855 DIBH breast-only treatment sessions. The DIBH agreement was evaluated using a programmable moving support. Dose agreement was evaluated for manual SGRT-assisted beam interruption and Halcyon arc beam interruption. RESULTS: Geometrical phantom agreement was < 0.4 mm. Couch and SGRT agreement for an anthropomorphic phantom resulted in 95% limits of agreement in Right-Left/Feet-Head/Posterior-Anterior (RL/FH/PA) directions of respectively ± 0.4/0.8/0.5 mm and ± 1.1/1.1/0.6 mm in the virtual and real isocenter. FB-SGRT-assisted patient positioning compared to CBCT positioning resulted in RL/FH/PA systematic differences of -0.1/0.1/2.0 mm with standard deviations of 2.7/2.8/2.4 mm. This mean systematic difference had three origins: a) couch sag/isocenter difference of ≤ 0.5 mm. b) Average reconstructed FB-CBCT images do not visually represent the average respiratory position. c) CBCT-based positioning focused on the inner thoracic interface, which can introduce a mean positioning difference between SGRT and CBCT. Manual SGRT-assisted beam interruption and arc interruptions resulted in mean gamma passing rates > 97% (0.5%/0.5 mm) and mean absolute differences < 0.3%. CONCLUSIONS: Accuracy was comparable with breast-only C-arm SGRT techniques, with different tradeoffs. Depending on the patient's morphology, real-time tracking accuracy in the real isocenter can be reduced. This study demonstrates possible discordances between SGRT and CBCT positioning for breast.