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BACKGROUND: Despite trimodality treatment, 10% to 20% of patients with esophageal cancer experience interval metastases after surgery. Restaging may identify patients who should not proceed to surgery, as well as a subgroup with limited metastases for whom long-term disease-control can be obtained. This study aimed to determine the proportion of patients with interval metastases after neoadjuvant chemoradiotherapy (nCRT) and to evaluate treatment and survival. METHODS: Patients who had cT2-4aN0-3M0 esophageal cancer treated with nCRT were identified from a trial database. Metastases detected up to 14 weeks after nCRT on 18F-FDG-PET/CT or during surgery were categorized as oligometastases (≤3 lesions located in one single organ or one extra-regional lymph node station) or as non-oligometastases. The primary outcome was the proportion of patients with metastases after nCRT. The secondary outcomes were overall survival (OS) and the site and treatment of metastases. RESULTS: Between 2013 and 2021, 973 patients received nCRT, and 10.3% had interval metastases. Of 100 patients, 30 (30%) had oligometastases, located mostly in non-regional lymph nodes (33.3%) or bones (26.7%). The median OS of this group was 13.8 months (95% confidence interval [CI] 9.2-27.1 months). Of 30 patients, 12 (40%) with oligometastases underwent potentially curative treatment, with a median OS of 22.8 months (95% CI 10.4-NA). The patients with non-oligometastases underwent mostly systemic therapy or BSC and had a median OS of 9 months (95% CI 7.4-10.9 months). CONCLUSIONS: Interval metastases were detected in about 10% of patients after nCRT, underscoring the importance of re-staging with 18F-FDG-PET/CT for those who proceed to surgery. A favorable survival might be accomplished for a subgroup of patients with oligometastases.
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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.
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BACKGROUND: Postoperative pancreatic fistula remains the leading cause of significant morbidity after pancreatoduodenectomy for pancreatic ductal adenocarcinoma. Preoperative chemoradiotherapy has been described to reduce the risk of postoperative pancreatic fistula, but randomized trials on neoadjuvant treatment in pancreatic ductal adenocarcinoma focus increasingly on preoperative chemotherapy rather than preoperative chemoradiotherapy. This study aimed to investigate the impact of preoperative chemotherapy and preoperative chemoradiotherapy on postoperative pancreatic fistula and other pancreatic-specific surgery related complications on a nationwide level. METHODS: All patients after pancreatoduodenectomy for pancreatic ductal adenocarcinoma were included in the mandatory nationwide prospective Dutch Pancreatic Cancer Audit (2014-2020). Baseline and treatment characteristics were compared between immediate surgery, preoperative chemotherapy, and preoperative chemoradiotherapy. The relationship between preoperative chemotherapy, chemoradiotherapy, and clinically relevant postoperative pancreatic fistula (International Study Group of Pancreatic Surgery grade B/C) was investigated using multivariable logistic regression analyses. RESULTS: Overall, 2,019 patients after pancreatoduodenectomy for pancreatic ductal adenocarcinoma were included, of whom 1,678 underwent immediate surgery (83.1%), 192 (9.5%) received preoperative chemotherapy, and 149 (7.4%) received preoperative chemoradiotherapy. Postoperative pancreatic fistula occurred in 8.3% of patients after immediate surgery, 4.2% after preoperative chemotherapy, and 2.0% after preoperative chemoradiotherapy (P = .004). In multivariable analysis, the use of preoperative chemoradiotherapy was associated with reduced risk of postoperative pancreatic fistula (odds ratio, 0.21; 95% confidence interval, 0.03-0.69; P = .033) compared with immediate surgery, whereas preoperative chemotherapy was not (odds ratio, 0.59; 95% confidence interval, 0.25-1.25; P = .199). Intraoperatively hard, or fibrotic pancreatic texture was most frequently observed after preoperative chemoradiotherapy (53% immediate surgery, 62% preoperative chemotherapy, 77% preoperative chemoradiotherapy, P < .001). CONCLUSION: This nationwide analysis demonstrated that in patients undergoing pancreatoduodenectomy for pancreatic ductal adenocarcinoma, only preoperative chemoradiotherapy, but not preoperative chemotherapy, was associated with a reduced risk of postoperative pancreatic fistula.
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Carcinoma Ductal Pancreático , Fístula Pancreática , Neoplasias Pancreáticas , Pancreaticoduodenectomia , Complicações Pós-Operatórias , Humanos , Pancreaticoduodenectomia/efeitos adversos , Fístula Pancreática/prevenção & controle , Fístula Pancreática/etiologia , Fístula Pancreática/epidemiologia , Feminino , Masculino , Carcinoma Ductal Pancreático/terapia , Carcinoma Ductal Pancreático/cirurgia , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/cirurgia , Pessoa de Meia-Idade , Idoso , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Países Baixos/epidemiologia , Terapia Neoadjuvante/métodos , Terapia Neoadjuvante/efeitos adversos , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Estudos Prospectivos , Cuidados Pré-Operatórios/métodosRESUMO
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 (18F-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 %.
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Adenocarcinoma , Neoplasias Esofágicas , Humanos , Quimioterapia de Indução/métodos , Esofagectomia/métodos , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/tratamento farmacológico , Terapia Neoadjuvante/métodos , Adenocarcinoma/cirurgia , Adenocarcinoma/tratamento farmacológico , Taxa de Sobrevida , Estudos Retrospectivos , Estadiamento de NeoplasiasRESUMO
BACKGROUND AND PURPOSE: Concurrent chemo-radiotherapy (CCRT) followed by adjuvant durvalumab is standard-of-care for fit patients with unresectable stage III NSCLC. Intensity modulated proton therapy (IMPT) results in different doses to organs than intensity modulated photon therapy (IMRT). We investigated whether IMPT compared to IMRT reduce hematological toxicity and whether it affects durvalumab treatment. MATERIALS AND METHODS: Prospectively collected series of consecutive patients with stage III NSCLC receiving CCRT between 06.16 and 12.22 (staged with FDG-PET-CT and brain imaging) were retrospectively analyzed. The primary endpoint was the incidence of lymphopenia grade ≥ 3 in IMPT vs IMRT treated patients. RESULTS: 271 patients were enrolled (IMPT: n = 71, IMRT: n = 200) in four centers. All patients received platinum-based chemotherapy. Median age: 66 years, 58 % were male, 36 % had squamous NSCLC. The incidence of lymphopenia grade ≥ 3 during CCRT was 67 % and 47 % in the IMRT and IMPT group, respectively (OR 2.2, 95 % CI: 1.0-4.9, P = 0.03). The incidence of anemia grade ≥ 3 during CCRT was 26 % and 9 % in the IMRT and IMPT group respectively (OR = 4.9, 95 % CI: 1.9-12.6, P = 0.001). IMPT was associated with a lower rate of Performance Status (PS) ≥ 2 at day 21 and 42 after CCRT (13 % vs. 26 %, P = 0.04, and 24 % vs. 39 %, P = 0.02). Patients treated with IMPT had a higher probability of receiving adjuvant durvalumab (74 % vs. 52 %, OR 0.35, 95 % CI: 0.16-0.79, P = 0.01). CONCLUSION: IMPT was associated with a lower incidence of severe lymphopenia and anemia, better PS after CCRT and a higher probability of receiving adjuvant durvalumab.
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Anemia , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Linfopenia , Terapia com Prótons , Radioterapia de Intensidade Modulada , Humanos , Masculino , Idoso , Feminino , Prótons , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Retrospectivos , Carcinoma Pulmonar de Células não Pequenas/terapia , Terapia com Prótons/efeitos adversos , Terapia com Prótons/métodos , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/etiologia , Linfopenia/etiologia , Anemia/etiologia , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodosRESUMO
BACKGROUND: Guidelines suggest that the serum carbohydrate antigen (CA19-9) level should be used when deciding on neoadjuvant treatment in patients with resectable and borderline resectable pancreatic ductal adenocarcinoma (hereafter referred to as pancreatic cancer). In patients with resectable pancreatic cancer, neoadjuvant therapy is advised when the CA19-9 level is 'markedly elevated'. This study investigated the impact of baseline CA19-9 concentration on the treatment effect of neoadjuvant chemoradiotherapy (CRT) in patients with resectable and borderline resectable pancreatic cancers. METHODS: In this post hoc analysis, data were obtained from two RCTs that compared neoadjuvant CRT with upfront surgery in patients with resectable and borderline resectable pancreatic cancers. The effect of neoadjuvant treatment on overall survival was compared between patients with a serum CA19-9 level above or below 500 units/ml using the interaction test. RESULTS: Of 296 patients, 179 were eligible for analysis, 90 in the neoadjuvant CRT group and 89 in the upfront surgery group. Neoadjuvant CRT was associated with superior overall survival (HR 0.67, 95 per cent c.i. 0.48 to 0.94; P = 0.019). Among 127 patients (70, 9 per cent) with a low CA19-9 level, median overall survival was 23.5 months with neoadjuvant CRT and 16.3 months with upfront surgery (HR 0.63, 0.42 to 0.93). For 52 patients (29 per cent) with a high CA19-9 level, median overall survival was 15.5 months with neoadjuvant CRT and 12.9 months with upfront surgery (HR 0.82, 0.45 to 1.49). The interaction test for CA19-9 level exceeding 500 units/ml on the treatment effect of neoadjuvant CRT was not significant (P = 0.501). CONCLUSION: Baseline serum CA19-9 level defined as either high or low has prognostic value, but was not associated with the treatment effect of neoadjuvant CRT in patients with resectable and borderline resectable pancreatic cancers, in contrast with current guideline advice.
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Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Terapia Neoadjuvante/efeitos adversos , Antígeno CA-19-9/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Pancreáticas/cirurgia , Adenocarcinoma/patologia , Carboidratos/uso terapêutico , Estudos Retrospectivos , Quimiorradioterapia , Neoplasias PancreáticasRESUMO
BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy is a standard treatment for potentially curable esophageal cancer. Active surveillance in patients with a clinically complete response (cCR) 12 weeks after nCRT is regarded as possible alternative to standard surgery. The aim of this study is to monitor the safety, adherence and effectiveness of active surveillance in patients outside a randomized trial. METHODS: This nationwide prospective cohort study aims to accrue operable patients with non-metastatic histologically proven adenocarcinoma or squamous cell carcinoma of the esophagus or esophagogastric junction. Patients receive nCRT and response evaluation consists of upper endoscopy with bite-on-bite biopsies, endoscopic ultrasonography plus fine-needle aspiration of suspicious lymph nodes and 18F-fluorodeoxyglucose positron emission tomography/computed tomography scan. When residue or regrowth of tumor in the absence of distant metastases is detected, surgical resection is advised. Patients with cCR after nCRT are suitable to undergo active surveillance. Patients can consult an independent physician or psychologist to support decision-making. Primary endpoint is the number and severity of adverse events in patients with cCR undergoing active surveillance, defined as complications from response evaluations, delayed surgery and the development of distant metastases. Secondary endpoints include timing and quality of diagnostic modalities, overall survival, progression-free survival, fear of cancer recurrence and decisional regret. DISCUSSION: Active surveillance after nCRT may be an alternative to standard surgery in patients with esophageal cancer. Similar to organ-sparing approaches applied in other cancer types, the safety and efficacy of active surveillance needs monitoring before data from randomized trials are available. TRIAL REGISTRATION: The SANO-2 study has been registered at ClinicalTrials.gov as NCT04886635 (May 14, 2021) - Retrospectively registered.
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Neoplasias Esofágicas , Conduta Expectante , Humanos , Estudos Prospectivos , Terapia Neoadjuvante/métodos , Quimiorradioterapia/métodos , Recidiva Local de Neoplasia , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patologia , Esofagectomia/métodosRESUMO
BACKGROUND: Oligoprogression (OPD) is defined as a condition where limited progression (1-3 metastases) is observed in patients undergoing systemic cancer treatment. In this study we investigated the impact of stereotactic body radiotherapy (SBRT) in patients with OPD from metastatic lung cancer. MATERIAL AND METHODS: Data from a cohort of consecutive patients with SBRT treated between June 2015 and August 2021 were collected. All extracranial metastatic sites of OPD from lung cancer were included. Dose regimens consisted of mainly 24 in 2 fractions, 30-51 Gy in 3 fractions, 30-55 Gy in 5 fractions, 52.5 Gy in 7 fractions and 44-56 Gy in 8 fractions. Kaplan-Meier method was used to calculate Overall Survival (OS), Local Control (LC), and Disease-Free Survival (DFS) from the start date of SBRT to the event. RESULTS: Sixty-three patients, 34 female and 29 males were included. Median age was 75 years (range 25-83). All patients received concurrent systemic treatment before the start of the SBRT: 19 chemotherapy (CT), 26 CT plus immunotherapy (IT) or Tyrosin kinase inhibitors (TKI) and 18 IT/TKI. SBRT was delivered to the lung (n = 29), mediastinal node (n = 9), bone (n = 7), adrenal gland (n = 19), other visceral metastases (1) and other node metastases (n = 4). After a median follow-up of 17 months, median OS was 23 months. LC was 93% at 1 year and 87% at 2 years. DFS was 7 months. According to our results, there was no statistically significant correlation between prognostic factors and OS after SBRT in OPD patients. CONCLUSIONS: Median DFS was 7 months, translating into the continuation of effective systemic treatment as other metastases grow slowly. In patients with oligoprogression disease, SBRT is a valid and efficient treatment that may enable postponing the switch of systemic line.
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Neoplasias Pulmonares , Radiocirurgia , Masculino , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Radiocirurgia/métodos , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias Pulmonares/patologiaRESUMO
BACKGROUND AND PURPOSE: In this phase I/II trial, non-progressive locally advanced pancreatic cancer (LAPC) patients after (modified)FOLFIRINOX therapy were treated with stereotactic body radiotherapy (SBRT) combined with heat-killed mycobacterium (IMM-101) vaccinations. We aimed to assess safety, feasibility, and efficacy of this treatment approach. MATERIALS AND METHODS: On five consecutive days, patients received a total of 40 Gray (Gy) of SBRT with a dose of 8 Gy per fraction. Starting two weeks prior to SBRT, they in addition received six bi-weekly intradermal vaccinations with one milligram of IMM-101. The primary outcomes were the number of grade 4 or higher adverse events and the one-year progression free-survival (PFS) rate. RESULTS: Thirty-eight patients were included and started study treatment. Median follow-up was 28.4 months (95 %CI 24.3 - 32.6). We observed one grade 5, no grade 4 and thirteen grade 3 adverse events, none related to IMM-101. The one-year PFS rate was 47 %, the median PFS was 11.7 months (95 %CI 11.0 - 12.5) and the median overall survival was 19.0 months (95 %CI 16.2 - 21.9). Eight (21 %) tumors were resected, of which 6 (75 %) were R0 resections. Outcomes were comparable with the outcomes of the patients from the previous LAPC-1 trial, in which LAPC patients were treated with SBRT, without IMM-101. CONCLUSION: Combination treatment with IMM-101 and SBRT was safe and feasible for non-progressive locally advanced pancreatic cancer patients after (modified)FOLFIRINOX. No improvement in the progression-free survival could be demonstrated by adding IMM-101 to SBRT.
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Neoplasias Pancreáticas , Radiocirurgia , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos de Viabilidade , Temperatura Alta , Quimioterapia de Indução , Micobactérias não Tuberculosas , Radiocirurgia/efeitos adversosRESUMO
Introduction: Stereotactic body radiotherapy (SBRT) reported excellent outcomes and a good tolerability profile in case of central lung tumors, as long as risk-adapted schedules were adopted. High grade toxicity was more frequently observed for tumors directly touching or overlapping the trachea, proximal bronchial tree (PBT), and esophagus. We aim to identify prognostic factors associated with survival for Ultra-Central (UC) tumors. Methods: We retrospectively evaluated patients treated with SBRT for primary or metastatic UC lung tumors. SBRT schedules ranged from 45 to 60 Gy. Results: A total number of 126 ultra-central lung tumors were reviewed. The Median follow-up time was 23 months. Median Overall Survival (OS) and Progression Free Survival (PFS) was 29.3 months and 16 months, respectively. Local Control (LC) rates at 1 and 2 were 86% and 78%, respectively. Female gender, age < 70 years, and tumor size < 5 cm were significantly associated with better OS. The group of patients with tumors close to the trachea but further away from the PBT also correlated with better OS. The acute G2 dysphagia, cough, and dyspnea were 11%, 5%, and 3%, respectively. Acute G3 dyspnea was experienced by one patient. Late G3 toxicity was reported in 4% of patients. Conclusion: risk-adaptive SBRT for ultra-central tumors is safe and effective, even if it remains a high-risk clinical scenario.
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BACKGROUND: Patients with locally advanced pancreatic cancer (LAPC) are treated with chemotherapy. In selected cases, stereotactic body radiotherapy (SBRT) can be added to the regimen. We hypothesized that adding an adjuvant containing a heat-killed mycobacterium (IMM-101) to SBRT may lead to beneficial immuno-modulatory effects, thereby improving survival. This study aims to investigate the safety of adding IMM-101 to SBRT and to investigate the immuno-modulatory effects of the combination treatment in the peripheral blood of LAPC patients. METHODS: LAPC patients were treated with SBRT (40 Gy) and six intradermal vaccinations of one milligram IMM-101. The primary endpoint was an observed toxicity rate of grade 4 or higher. Targeted gene-expression profiling and multicolor flow cytometry were performed for longitudinal immune-monitoring of the peripheral blood. RESULTS: Twenty patients received study treatment. No treatment-related adverse events of grade 4 or higher occurred. SBRT/IMM-101 treatment induced a transient decrease in different lymphocyte subsets and an increase in CD14+CD16-CD11b+HLA-DRlow myeloid-derived suppressor cells. Importantly, treatment significantly increased activated ICOS+, HLA-DR+ and Ki67+PD1+ T and NK cell frequencies. This was not accompanied by increased levels of most inhibitory markers, such as TIM-3 and LAG-3. CONCLUSIONS: Combination therapy with SBRT and a heat-killed mycobacterium vaccine was safe and had an immune-stimulatory effect.
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Background and purpose: Stereotactic body radiotherapy (SBRT) has been proven to be beneficial for several disease sites in the (lower) abdomen. However, the quality of the treatment plan, based on a single planning computed tomography (CT), can be compromised due to large inter-fraction motion of the target and organs at risk (OARs) in this anatomical region. The aim of this study was to investigate the feasibility of online adaptive SBRT treatments on a robotic radiosurgery system and to record estimated total treatment times. Materials and methods: For two disease sites, locally advanced pancreatic cancer (LAPC) and oligometastatic lymph nodes, four patients with repeat CTs were included in the feasibility study. Quick treatment plan templates were generated based on the planning CT and validated by running them on the plan and fraction CTs. For two cases a dummy run was performed and the individual steps were timed. Dose delivery was the largest contributor to the total treatment time, followed by contour adaptation. Results: Running the quick plan templates resulted in plans similar to unrestricted plans, obeying the OAR constraints. The dummy runs showed that online adaptive treatments were completed in 64 to 83 min respectively for oligometastases and LAPC, comparable to other clinically available solutions. Conclusions: This study showed the feasibility of online re-planning for two challenging disease sites within a clinically acceptable time frame on a robotic radiosurgery system, making use of commercially available elements that are not integrated by the vendor.
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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/m2), leucovorin (200 mg/m2), oxaliplatin (85 mg/m2) and docetaxel (50 mg/m2). 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/m2), 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.
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Purpose: To determine the dosimetric impact of using unedited autocontours in daily plan adaptation of patients with locally advanced pancreatic cancer (LAPC) treated with stereotactic body radiotherapy using tumor tracking. Materials and Methods: The study included 98 daily CT scans of 35 LAPC patients. All scans were manually contoured (MAN), and included the PTV and main organs-at-risk (OAR): stomach, duodenum and bowel. Precision and MIM deformable image registration (DIR) methods followed by contour propagation were used to generate autocontour sets on the daily CT scans. Autocontours remained unedited, and were compared to MAN on the whole organs and at 3, 1 and 0.5 cm from the PTV. Manual and autocontoured OAR were used to generate daily plans using the VOLO™ optimizer, and were compared to non-adapted plans. Resulting planned doses were compared based on PTV coverage and OAR dose-constraints. Results: Overall, both algorithms reported a high agreement between unclipped MAN and autocontours, but showed worse results when being evaluated on the clipped structures at 1 cm and 0.5 cm from the PTV. Replanning with unedited autocontours resulted in better OAR sparing than non-adapted plans for 95% and 84% plans optimized using Precision and MIM autocontours, respectively, and obeyed OAR constraints in 64% and 56% of replans. Conclusion: For the majority of fractions, manual correction of autocontours could be avoided or be limited to the region closest to the PTV. This practice could further reduce the overall timings of adaptive radiotherapy workflows for patients with LAPC.
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Purpose: The aim of this prospective cohort study was to determine the outcome and quality of life (QoL) for patients with brain metastases treated with whole-brain radiotherapy (WBRT). Materials and Methods: WBRT was given to 162 patients. Treatment outcome was reported through telephone consultation at four and eight weeks after the last fraction of the treatment. Treatment outcome was scored as a benefit when patients reported positively on the question whether radiotherapy of the whole brain did relieve their complaints. Patients who scored the treatment as beneficial were categorized as responders. The European Organization for Research and Treatment of Cancer (EORTC) questionnaire QLQ-C15-PAL was scored at day 0 and eight weeks after the last fraction of WBRT. Results: Patients who were alive after 2 months and reported benefit from treatment had a median survival of 8.1 months compared with 2.9 months for patients who reported no benefit. Forty-three patients died within two months (27%). Median overall survival was 3.5 months. Improvement of neurological symptoms was the most commonly reported benefit of the treatment. The responders had significantly better sleep (p = 0.032) and were less tense (p = 0.014). The nonresponders were also less tense (p = 0.042), but had less appetite (p = 0.023), felt weaker (p = 0.011), and experienced more fatigue (p = 0.001). Conclusions: WBRT is effective in a selected group of patients. Forty-nine percent of the patients surviving two months reported benefit from the treatment, resulting in a significantly increased survival rate for this group. However, 27% of patients died within two months. QoL increased in responders, but decreased in nonresponders.
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Neoplasias Encefálicas , Qualidade de Vida , Encéfalo , Neoplasias Encefálicas/radioterapia , Humanos , Medidas de Resultados Relatados pelo Paciente , Estudos Prospectivos , Encaminhamento e Consulta , TelefoneRESUMO
PURPOSE: To analyze the effect of radiation dose escalation to the primary tumor on local tumor control in definitive chemoradiation (dCRT) for patients with esophageal cancer. PATIENTS AND METHODS: Patients with medically inoperable and/or irresectable esophageal carcinoma, referred for dCRT, were randomly assigned between a standard dose (SD) of 50.4 Gy/1.8 Gy for 5.5 weeks to the tumor and regional lymph nodes and a high dose (HD) up to a total dose of 61.6 Gy to the primary tumor. Chemotherapy consisted of courses of concurrent carboplatin (area under the curve 2) and paclitaxel (50 mg/m2) in both arms once a week for 6 weeks. The primary end point was local progression-free survival. RESULTS: Between September 2012 and June 2018, 260 patients were included. Squamous cell carcinoma (SCC) was present in 61% of patients, and 39% had adenocarcinoma (AC). Radiation treatment was completed by 94%, and 85% had at least five courses of chemotherapy. The median follow-up time for all patients was 50 months. The 3-year local progression-free survival (LPFS) was 70% in the SD arm versus 73% in the HD arm (not significant). The LPFS for SCC and AC was 75% versus 79% and 61% versus 61% for SD and HD, respectively (not significant). The 3-year locoregional progression-free survival was 52% and 59% for the SD and HD arms, respectively (P = .08). Overall, grade 4 and 5 common toxicity criteria were 12% and 5% in the SD arm versus 14% and 10% in the HD arm, respectively (P = .15). CONCLUSION: In dCRT for esophageal cancer, radiation dose escalation up to 61.6 Gy to the primary tumor did not result in a significant increase in local control over 50.4 Gy. The absence of a dose effect was observed in both AC and SCC.
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Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/mortalidade , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/terapia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carboplatina/administração & dosagem , Relação Dose-Resposta à Radiação , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Prognóstico , Taxa de SobrevidaRESUMO
BACKGROUND: The added value of radiotherapy following neoadjuvant FOLFIRINOX chemotherapy in patients with resectable or borderline resectable pancreatic cancer ((B)RPC) is unclear. The objective of this meta-analysis was to compare outcomes of patients who received neoadjuvant FOLFIRINOX alone or combined with radiotherapy. METHODS: A systematic literature search was performed in Embase, Medline (ovidSP), Web of Science, Scopus, Cochrane, and Google Scholar. The primary endpoint was pooled median overall survival (OS). Secondary endpoints included resection rate, R0 resection rate, and other pathologic outcomes. RESULTS: We included 512 patients with (B)RPC from 15 studies, of which 7 were prospective nonrandomized studies. In total, 351 patients (68.6%) were treated with FOLFIRINOX alone (8 studies) and 161 patients (31.4%) were treated with FOLFIRINOX and radiotherapy (7 studies). The pooled estimated median OS was 21.6 months (range 18.4-34.0 months) for FOLFIRINOX alone and 22.4 months (range 11.0-37.7 months) for FOLFIRINOX with radiotherapy. The pooled resection rate was similar (71.9% vs. 63.1%, p = 0.43) and the pooled R0 resection rate was higher for FOLFIRINOX with radiotherapy (88.0% vs. 97.6%, p = 0.045). Other pathological outcomes (ypN0, pathologic complete response, perineural invasion) were comparable. CONCLUSIONS: In this meta-analysis, radiotherapy following neoadjuvant FOLFIRINOX was associated with an improved R0 resection rate as compared with neoadjuvant FOLFIRINOX alone, but a difference in survival could not be demonstrated. Randomized trials are needed to determine the added value of radiotherapy following neoadjuvant FOLFIRINOX in patients with (B)PRC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Pancreáticas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fluoruracila/uso terapêutico , Humanos , Irinotecano , Leucovorina/uso terapêutico , Terapia Neoadjuvante , Oxaliplatina , Neoplasias Pancreáticas/tratamento farmacológico , Estudos ProspectivosRESUMO
PURPOSE: To study the trade-offs of three online strategies to adapt treatment plans of patients with locally advanced pancreatic carcinoma (LAPC) treated using the CyberKnife with tumor tracking. METHODS AND MATERIALS: A total of 35 planning computed tomography scans and 98 daily in-room computed tomography scans were collected from 35 patients with LAPC. Planned dose distributions, optimized with VOLO, were evaluated on manually contoured daily anatomies to collect daily doses. Three strategies were tested to adapt treatment plans: (1) unrestricted full replanning using a patient-specific plan template, (2) time-restricted replanning on organs at risk (OARs) within 3 cm from the planning target volume (PTV) structure, and (3) dose realignment optimization to stay within OAR constraints. Dose distributions resulting from each plan adaptation strategy were dosimetrically compared by means of gross tumor volume (GTV), PTV coverage, and OAR tolerances. RESULTS: Planned doses did not result in dose-constraint violations for 28 of 98 daily anatomies. None of the suggested plan adaptation strategies improved planned doses significantly for this subset. For 70 of the 98 reported violations, the median (interquartile range) PTV coverage of the planned dose was 84% (76% to 86%). After plan adaptation, unrestricted replanning achieved clinically acceptable plans in 93% of these fractions, time-restricted replanning in 90%, and dose realignment in 74%, at median computational times of 8.5, 3, and 0.5 minutes. Over all 98 fractions, PTV coverage was reduced: -1% (-3% to 1%), -2% (-5% to 0%), and -2% (-8% to 0%) after each strategy, respectively. In 3 of 70 fractions, none of the suggested strategies achieved clinically acceptable OAR dose volumes. CONCLUSIONS: Unrestricted replanning was the most time-consuming method but reached the highest number of successfully adapted plans. Time-restricted replanning and dose realignment resulted in a high number of plans within dose constraints. Depending on the resources available, an adaptive strategy can be selected for each patient to address the specific anatomic challenges on the treatment day. The increase in the complexity of the strategy corresponds with an increasing number of successfully adapted plans.
Assuntos
Neoplasias Pancreáticas/radioterapia , Radiocirurgia/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Órgãos em Risco , Dosagem RadioterapêuticaRESUMO
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.