Search

Definitive chemoradiotherapy (dCRT) is a potentially curative therapy for esophageal cancer. As indications for dCRT differ widely, it is challenging to draw conclusions on outcomes and survival. The aim of this study was to evaluate overall survival (OS) and recurrence patterns according to indications for treatment. Patients who underwent dCRT (50.4 Gy concomitant with carboplatin/paclitaxel) for esophageal cancer between 2012 and 2022 were identified. Indications for dCRT were: cervical tumor, irresectable disease, unfit for surgery, and patient and/or physician preference. The primary endpoint was OS calculated with the Kaplan–Meier method. Secondary endpoints included the proportion of patients that completed the dCRT regimen, 30- and 90-day mortality, and disease recurrence. One hundred and fifty-seven patients were included (72.6% esophageal squamous cell carcinoma) with a median follow-up of 20 months (IQR 10.0–43.9). The full dCRT regimen was completed by 116 patients (73.9%). Thirty- and 90-day mortality were 2.5% and 8.3%, respectively. Median and 5-year OS for all patients were 22.9 months (95% CI 18.0–27.9) and 31.4%, respectively. The median OS per indication was 23.7 months (95% CI 6.5–40.8) for patients with cervical tumors, 10.9 months (95% 0.0–23.2) for irresectable disease, 28.2 months (95% CI 12.3–44.0) for unfit patients, and 22.9 months (95% CI 15.4–30.5) for patients' preference for dCRT (P  = 0.11). Disease recurrence was observed in 74 patients (46%), located locoregionally (46%), distant (19%), or combined (35%). Patients who underwent dCRT had a 5-year OS of 31.4%, but OS differed according to indications for treatment with patients who had irresectable disease having the worst prognosis. [ABSTRACT FROM AUTHOR]

Background: Recent developments in esophageal cancer treatment, including studies exploring active surveillance following chemoradiotherapy, have led to a need for clear terminology and definitions regarding different multimodal treatment options. Objective: The aim of this study was to reach worldwide consensus on the definitions and semantics of multimodal esophageal cancer treatment. Methods: In total, 72 experts working in the field of multimodal esophageal cancer treatment were invited to participate in this Delphi study. The study comprised three Delphi surveys sent out by email and one online meeting. Input for the Delphi survey consisted of terminology obtained from a systematic literature search. Participants were asked to respond to open questions and to indicate whether they agreed or disagreed with different statements. Consensus was reached when there was ≥75% agreement among respondents. Results: Forty-nine of 72 invited experts (68.1%) participated in the first online Delphi survey, 45 (62.5%) in the second survey, 21 (46.7%) of 45 in the online meeting, and 39 (86.7%) of 45 in the final survey. Consensus on neoadjuvant and definitive chemoradiotherapy with or without surgery was reached for 27 of 31 items (87%). No consensus was reached on follow-up after treatment with definitive chemoradiotherapy. Conclusion(s): Consensus was reached on most statements regarding terminology and definitions of multimodal esophageal cancer treatment. Implementing uniform criteria facilitates comparison of studies and promotes international research collaborations. [ABSTRACT FROM AUTHOR]

Background and purpose: To review available data on toxicity during and/or after treatment of abdominal-pelvic lymph node oligometastases (A-P LN) with stereotactic body radiation therapy (SBRT) and to provide an overview of adverse events and its relation to dose or fractionation. Material and methods: For this systematic review, we searched MEDLINE, Embase, Web of Science Core Collection, and CINAH for studies published between the database inception and October 3rd, 2023. Inclusion criteria were (1) patients with 1-5 A-P LN oligometastases, (2) treatment with SBRT to a median prescribed dose of =55 Gy BED10, and (3) description of acute and/or late toxicity. There were no language or date restrictions. Results: A total of 35 studies, including 1,512 patients, were selected. Late grade 3 and 4 adverse events occurred in 0.6% and 0.1% of the patients treated for A-P LN oligometastases. All late adverse events grade = 3 occurred after treatment of the tumor with a minimum BED10 of 72 Gy. Of the 11 patients with severe late toxicity, five patients were re-irradiated. Late grade 2 and 1 toxicity was reported in 3.4% and 8.3% of the patients. Acute toxicity grades 4, 3, 2, and 1 occurred in 0.1%, 0.2%, 4.4%, and 19.8% of the patients, respectively. Interpretation: SBRT for A-P LN oligometastases show low toxicity rates. Nearly 50% of late adverse events = grade 3 were associated with re-irradiation. [ABSTRACT FROM AUTHOR]

Introduction: Patients with limited metastatic/advanced esophageal cancer not amenable for neoadjuvant therapy plus surgery have a poor prognosis and often receive palliative care. Alternatively, induction chemotherapy with response evaluation can be considered and in some patients surgery with curative intent may become feasible. The aim of this study was to evaluate the outcomes of patients treated with induction chemotherapy and to identify patient and/or tumor characteristics associated with survival., Material and Methods: Patients with esophageal or junctional cancer who underwent induction chemotherapy between 2005 and 2021 were identified from an institutional database of a tertiary referral center. Response to therapy was assessed by ( 18 F-FDG PET)/CT. Response to therapy and treatment options, including surgery or palliation, were discussed in the multidisciplinary tumor board. Overall survival (OS) was calculated using the Kaplan Meier method. Uni- and multivariable analyses were performed to identify prognostic factors for survival., Results: 238 patients were identified. The majority had esophageal adenocarcinoma (68.9 %) and were treated with a taxane/platinum-based chemotherapy (79.4 %). Response evaluation was performed in 233 patients and 154 of 238 patients (64.7 %) underwent surgical exploration. Resection was performed in 127 patients (53.4 %) resulting in a median and 5-year OS of 26.3 months (95 % CI 18.8-33.8) and 29.6 %, respectively. Presence of T4b (HR = 2.01, 95 % CI 1.02-3.92) and poorly differentiated tumor (HR = 1.45, 95 % CI 1.02-2.10) was associated with worse survival (p = 0.04)., Conclusion: In carefully selected patients with advanced disease not amenable for standard curative treatment, induction chemotherapy followed by esophagectomy may result in a 5-year overall survival of approximately 30 %., (© 2024 Published by Elsevier Ltd.)

Introduction: Clear guidelines for colorectal lung metastasis (LM) treatment are not available. This study aimed to provide insight into the treatment strategies and efficacy of local and systemic therapy in patients with LM eligible for (potentially) curative treatment., Methods: This was a retrospective study of patients with ≤5 LM discussed in two tertiary referral centers. Patient and tumor characteristics were compared between treatment groups. Treatment strategies were compared between centers and survival data between treatment groups, local treatment modalities, and treating centers., Results: Ninety-two patients (median 2 LMs) were included. Seventy-one (77%) patients underwent local treatment (17 surgery, 13 ablation, 38 radiotherapy, 3 combination of local treatments) and 21 (23%) with systemic therapy alone. The latter group more frequently had extrapulmonary metastases (81.0% vs. 26.8%, p < 0.001) and synchronous presentation of LM (23.8% vs. 7.0%, p = 0.045). Choice of local versus systemic therapy and time to start treatment after diagnosis (median 109 days, IQR 44-240 vs. 88 days, IQR 53-168) were comparable between centers. Three-year survival rates did not differ between treatment groups, local treatment modalities, or treating centers., Conclusion: Treatment strategies and oncological outcomes were rather similar between centers. Survival outcomes were not different between locally and systemically treated patients., (© 2024 S. Karger AG, Basel.)

Background: FLOT and CROSS are effective neoadjuvant regimens for esophageal cancer patients. Chemotherapy (FLOT) is aimed to have merely a systemic effect whereas neoadjuvant chemoradiotherapy (CROSS) achieves good locoregional response with clinically complete response (cCR) rates up to 33% [1]. The aim of the present study is to assess safety and feasibility of dual therapy (FLOT-CROSS) in patients with oligometastases., Methods: This phase-II single-center, single-arm, intervention study includes patients with oligometastatic adenocarcinoma of the esophagus or esophagogastric junction. Patients will be treated with four biweekly cycles of FLOT, consisting of intravenous fluorouracil (2600 mg/m 2 ), leucovorin (200 mg/m 2 ), oxaliplatin (85 mg/m 2 ) and docetaxel (50 mg/m 2 ). Response evaluation by CT-scan will be performed 4-6 weeks after completion of FLOT. In case of regression or stable disease according to RECIST criteria (v.1.1), patients will receive additional CROSS, consisting of five weekly cycles of intravenous carboplatin (AUC 2) and paclitaxel (50 mg/m 2 ), with concurrent 41.4 Gy radiotherapy, in 23 daily fractions of 1.8 Gy [2]. Response evaluation by endoscopy with biopsies, endoscopic ultrasonography and CT-scan will be performed 4-6 weeks after completion of CROSS. Primary endpoint is tolerability of FLOT-CROSS, defined as the proportion of patients who complete the full regimen. Secondary endpoints include disease control rate, objective response rate, overall survival and progression-free survival. In total, 20 patients will be included., Discussion: If patients are able to complete and tolerate FLOT-CROSS, this regimen should be tested in a phase-III trial and as neoadjuvant treatment in patients with locally advanced non-metastatic esophageal or junctional adenocarcinoma., Competing Interests: BM: Research funding 10.13039/100004339Sanofi, Consultant 10.13039/501100011725Servier, Lilly, J. Jan B. van Lanschot: Research funding 10.13039/501100001826ZonMw and KWF, All remaining authors have declared no conflicts of interest., (© 2022 The Authors.)

Introduction: Local treatment of metastases is frequently performed in patients with multiorgan metastatic colorectal carcinoma (mCRC) analogous to selected patients with oligometastatic disease for whom this is standard of care. The ORCHESTRA trial (NCT01792934) was designed to prospectively evaluate overall survival benefit from tumor debulking in addition to chemotherapy in patients with multiorgan mCRC. Here, we report the preplanned safety and feasibility evaluation after inclusion of the first 100 patients., Methods: Patients were eligible if at least 80% tumor debulking was deemed feasible by resection, radiotherapy and/or thermal ablative therapy. In case of clinical benefit after three or four cycles of respectively 5-fluorouracil/leucovorin or capecitabine and oxaliplatin ± bevacizumab patients were randomized to tumor debulking followed by chemotherapy in the intervention arm, or standard treatment with chemotherapy., Results: Twelve patients dropped out prior to randomization for various reasons. Eighty-eight patients were randomized to the standard (n = 43) or intervention arm (n = 45). No patients withdrew after randomization. Debulking was performed in 82% (n = 37). Two patients had no lesions left to treat, five had progressive disease, and one patient died prior to local treatment. In 15 patients (40%) 21 serious adverse events related to debulking were reported. Postoperative mortality was 2.7% (n = 1). After debulking chemotherapy was resumed in 89% of patients., Conclusion: Tumor debulking is feasible and does not prohibit administration of palliative chemotherapy in the majority of patients with multiorgan mCRC, despite the occurrence of serious adverse events related to local treatment., Implications for Practice: This first prospective randomized trial on tumor debulking in addition to chemotherapy shows that local treatment of metastases is feasible in patients with multiorgan metastatic colorectal cancer and does not prohibit administration of palliative systemic therapy, despite the occurrence of serious adverse events related to local treatment. The trial continues accrual, and overall survival (OS) data and quality of life assessment are collected to determine whether the primary aim of >6 months OS benefit with preserved quality of life will be met. This will support evidence-based decision making in multidisciplinary colorectal cancer care and can be readily implemented in daily practice., (© 2020 The Authors. The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.)

Purpose: This article reports on the integration of a sliding-gantry CT-on-rails with a robotic linear accelerator., Methods: The system consists of a SOMATOM Definition AS CT scanner (Siemens Healthcare, Forchheim, Germany) and a CyberKnife M6 FIM (Accuray, Inc., Sunnyvale, CA, USA). Additional movement programs were implemented in the robotic treatment table (RoboCouch, Accuray Inc.) to move between CT and treatment position. Acceptance testing was performed on the CT scanner according to AAPM83 guidelines, as well as safety tests for collision avoidance and electromagnetic (EM) compatibility. For the first clinical application of the system, daily dose was evaluated in five pancreas SBRT patients. A second envisioned use is the optimal alignment of the treatment beams to soft-tissue targets without the use of implanted fiducials. To this end, an offset vector feature has been implemented, which shifts the treatment center according to the daily position of the tumor relative to the spine (established by a CT scan). This offset can be applied by either moving the treatment couch (physical couch shift) or by moving the CyberKnife robot (virtual couch shift). An End-to-End (E2E) test was specifically designed to evaluate the accuracy of this feature using the Xsight Lung Tracking Phantom (Computerized Imaging Reference Systems, Inc., Norfolk, VA, USA). The position of the tumor with respect to the spine was varied by moving the insert inside the phantom and a CT scan was made for each position. The treatment plan was subsequently delivered to the phantom employing spine tracking. The test was repeated four times for a physical couch shift and four times for a virtual couch shift., Results: All acceptance, safety and EM compatibility testing was successful. For the first pancreas SBRT patients treated using daily CT imaging, the volume of stomach, duodenum, or small bowel receiving >35 Gy was found to increase or remain constant during treatment; however, the clinical constraint of 5 cc was not violated. For the offset vector E2E test, the reference accuracy (without any tumor shift) was (0.74, -0.61, -0.33) mm in the inferior, left, and anterior direction respectively. The difference in deviation with respect to the reference was (-0.1 ± 0.15, 0.01 ± 0.16, -0.17 ± 0.25) mm, when applying a physical couch shift. With a virtual couch shift, the deviations were (0.02 ± 0.15, 0.06 ± 0.23, -0.4 ± 0.31) mm., Conclusions: The first combination of a CyberKnife treatment unit with a sliding-gantry CT scanner is operational in our department enabling future developments toward image-guided online-adaptive SBRT supported by diagnostic-quality CT imaging., (© 2017 American Association of Physicists in Medicine.)

Background: The CARTS study is a multicenter feasibility study, investigating the role of rectum saving surgery for distal rectal cancer., Methods/design: Patients with a clinical T1-3 N0 M0 rectal adenocarcinoma below 10 cm from the anal verge will receive neoadjuvant chemoradiation therapy (25 fractions of 2 Gy with concurrent capecitabine). Transanal Endoscopic Microsurgery (TEM) will be performed 8 - 10 weeks after the end of the preoperative treatment depending on the clinical response.Primary objective is to determine the number of patients with a (near) complete pathological response after chemoradiation therapy and TEM. Secondary objectives are the local recurrence rate and quality of life after this combined therapeutic modality. A three-step analysis will be performed after 20, 33 and 55 patients to ensure the feasibility of this treatment protocol., Discussion: The CARTS-study is one of the first prospective multicentre trials to investigate the role of a rectum saving treatment modality using chemoradiation therapy and local excision. The CARTS study is registered at clinicaltrials.gov (NCT01273051).

Purpose: Compared with many small circular beams used in CyberKnife treatments, beam's eye view-shaped fields are generally more time-efficient for dose delivery. However, beam's eye view-shaping devices, such as a mini-multileaf collimator (mMLC), are not presently available for CyberKnife, although a variable-aperture collimator (Iris, 12 field diameters; 5-60 mm) is available. We investigated whether the Iris can mimic noncoplanar mMLC treatments using a limited set of principal beam orientations (nodes) to produce time-efficient treatment plans., Methods and Materials: The data from 10 lung cancer patients and the beam-orientation optimization algorithm "Cycle" were used to generate stereotactic treatment plans (3 × 20 Gy) for a CyberKnife virtually equipped with a mMLC. Typically, 10-16 favorable beam orientations were selected from 117 available robot node positions using beam's eye view-shaped fields with uniform fluence. Second, intensity-modulated Iris plans were generated by inverse optimization of nonisocentric circular candidate beams targeted from the same nodes selected in the mMLC plans. The plans were evaluated using the mean lung dose, lung volume receiving ≥20 Gy, conformality index, number of nodes, beams, and monitor units, and estimated treatment time., Results: The mMLC plans contained an average of 12 nodes and 11,690 monitor units. For a comparable mean lung dose, the Iris plans contained 12 nodes, 64 beams, and 21,990 monitor units. The estimated fraction duration was 12.2 min (range, 10.8-13.5) for the mMLC plans and 18.4 min (range, 12.9-28.5) for the Iris plans. In contrast to the mMLC plans, the treatment time for the Iris plans increased with an increasing target volume. The Iris plans were, on average, 40% longer than the corresponding mMLC plans for small targets (<80 cm(3)) and ≤121% longer for larger targets. For a comparable conformality index, similar results were obtained., Conclusion: For stereotactic lung irradiation, time-efficient and high-quality plans were obtained for robotic-controlled noncoplanar treatments using a mMLC. Iris is a time-efficient alternative for small targets, with similar or better plan quality., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background and Purpose: To investigate the efficacy and toxicity of a short intensive Uracil/Tegafur (UFT) based chemoradiotherapy scheme combined with celecoxib in locally advanced pancreatic cancer., Material and Methods: The Academic Medical Centre, Amsterdam and the Erasmus Medical Centre, Rotterdam enrolled 83 eligible patients with unresectable pancreatic cancer in a prospective multicentre phase II study. Median age was 62 years, median tumour size 40 mm and the majority of the patients (85%) had pancreatic head cancers. Treatment consisted of 20×2.5 Gy radiotherapy combined with UFT 300 mg/m(2) per day, leucovorin (folinic acid) 30 mg and celecoxib 80 0mg for 28 days concomitant with radiotherapy. Four patients were lost to follow-up., Results: Full treatment compliance was achieved in 55% of patients, 80% received at least 3 weeks of treatment. No partial or complete response was observed. Median survival was 10.6 months and median time to progression 6.9 months. Toxicity was substantial with 28% grades III and IV gastro-intestinal toxicity and two early toxic deaths., Conclusions: Based on the lack of response, the substantial toxicity of mainly gastro-intestinal origin and the reported mediocre overall and progression free survival, we cannot advise our short intensive chemoradiotherapy schedule combined with celecoxib as the standard treatment., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

A total of 11 patients with recurrent rectal cancer who had been previously irradiated were treated with preoperative reirradiation (median dose 30Gy), surgery and IORT. This treatment was related with high morbidity, a short pain-free survival (5 months) and poor local control (27% after 3 years), although some patients have long-term distant control and survival.