Induction Chemoradiotherapy Research Articles

Efficacy and safety of different radiotherapy doses in neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer: A retrospective study.

This study aims to compare the efficacy and safety of neoadjuvant chemoradiotherapy (nCRT) with different radiotherapy doses (45Gy and 50.4Gy) in patients with locally advanced rectal cancer (LARC). Herein, 120 patients with LARC were retrospectively enrolled between January 2016 and June 2021. All patients underwent two courses of induction chemotherapy (XELOX), chemoradiotherapy, and total mesorectum excision (TME). A total of 72 patients received a radiotherapy dose of 50.4 Gy, while 48 patients received a dose of 45 Gy. Surgery was then performed within 5-12 weeks following nCRT. There was no statistically significant difference between the baseline characteristics of the two groups. The rate of good pathological response in the 50.4Gy group was 59.72% (43/72), while in the 45Gy group achieved 64.58% (31/48) (P>0.05). The disease control rate (DCR) in the 50.4Gy group was 88.89% (64/72), compared to 89.58% (43/48) in the 45Gy group (P>0.05). The incidence of adverse reactions for radioactive proctitis, myelosuppression, and intestinal obstruction or perforation differed significantly between the two groups (P<0.05). The anal retention rate in the 50.4Gy group was significantly higher in contrast to the 45Gy group (P<0.05). Patients receiving a radiotherapy dose of 50.4Gy have a better anal retention rate but also a higher incidence of adverse events such as radioactive proctitis, myelosuppression, and intestinal obstruction or perforation, and a comparable prognosis to patients treated with a radiotherapy dose of 45Gy.

Essential updates 2020/2021: Recent topics in surgery and perioperative therapy for esophageal cancer.

In this review, we focused on four topics, namely, minimally invasive esophagectomy (MIE), robot-assisted minimally invasive esophagectomy (RAMIE), conversion and salvage surgery, and neoadjuvant and adjuvant therapy, based on notable reports published in the years 2020 and 2021. It seems that while the short-term outcomes of minimally invasive Ivor Lewis esophagectomy (MIE-IL) were better than those of open Ivor Lewis esophagectomy (OE-IL), there were no significant differences in the long-term outcomes between MIE-IL and OE-IL. Similarly, the short-term outcomes of minimally invasive McKeown esophagectomy (MIE-MK) were better than those of open McKeown esophagectomy (OE-MK), while there were no significant differences in the long-term outcomes between MIE-MK and OE-MK. Furthermore, the short-term outcomes of robot-assisted minimally invasive Ivor Lewis esophagectomy (RAMIE-IL) were superior to those of completely minimally invasive Ivor Lewis esophagectomy (CMIE-IL). On the other hand, there were advantages and disadvantages in relation to the short-term outcomes of robot-assisted minimally invasive McKeown esophagectomy (RAMIE-MK) as compared with completely minimally invasive McKeown esophagectomy (CMIE-MK). However, there were no significant differences in the long-term outcomes between RAMIE-MK and CMIE-MK. Further research is needed to evaluate of short-term and long-term outcomes of transmediastinal esophagectomy with and without robotic assistance. Both induction chemotherapy and induction chemoradiotherapy appear to be promising to secure a higher rate of conversion surgery. Neoadjuvant chemoimmunotherapy and chemoimmunoradiotherapy have shown promising results and are expected as new powerful therapies.

The beginning of a new era in induction treatment for operable non-small cell lung cancer: a narrative review.

The survival benefit of induction therapy for non-small cell lung cancer (NSCLC) remains controversial. Recently, the outcomes of systemic therapy for NSCLC have dramatically changed with the advent of molecular target drugs and immune checkpoint inhibitors (ICIs). The present review was conducted to investigate the outcomes of induction therapy with reference to randomized control trials (RCTs). We reviewed RCTs and ongoing clinical trials between 1990 and 2022 using relevant databases: PubMed, Web of Science, and EMBASE database. We investigated the outcomes of induction therapy. Induction therapy was associated with longer overall survival in comparison to surgery alone in several RCTs for stage III disease. However, its benefit in early-stage (I-II) disease was unclear. Regarding induction chemotherapy and chemoradiotherapy, the safety and survival outcomes did not differ between the two arms. Epidermoid growth factor receptor (EGFR) tyrosine kinase inhibitors as induction therapy in patients with proven EGFR mutations may be a sufficient choice for the improvement of overall survival. In ongoing single arm clinical trials and a randomized control study, the administration of ICIs as induction therapy was associated with a good pathological response and satisfactory safety, which will lead to a better survival outcome. Long-term observation is needed to evaluate the toxicity and survival impact of induction therapy with ICIs. Induction chemotherapy and EGFR-TKIs for stage IIIA NSCLC may contribute to the improvement of survival outcomes although the effect of systemic therapy on stage I-II remains controversial. ICIs may be considered as a valuable treatment option because of their feasibility and safety for induction therapy.

Multimodal Treatment Strategies to Improve the Prognosis of Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma: A Narrative Review.

Esophageal cancer is the seventh most common malignancy and sixth most common cause of cancer-related death globally. Esophageal squamous cell carcinoma (ESCC) with aortic or tracheal invasion is considered unresectable, and has an extremely poor prognosis; its standard treatment is definitive chemoradiotherapy (dCRT). In recent years, induction chemotherapy (ICT) has been reported to yield high response rates for locally advanced ESCC, and the efficacy and safety of ICT followed by conversion surgery (CS) have been investigated. Multimodal treatment, combining surgery with induction chemoradiotherapy (ICRT) or ICT, is necessary to improve ESCC prognosis. CS is generally performed for locally advanced ECC after ICRT or ICT when tumor downstaging is achieved, although its prognostic benefit remains controversial. The Japan Clinical Oncology Group (JCOG) has conducted a three-arm phase III randomized controlled trial (JCOG1510) to confirm the superiority of DCF (docetaxel, cisplatin, and 5-fluorouracil) ICT, over conventional dCRT, among patients with initially unresectable ESCC. In recent years, researchers have reported favorable outcomes of induction therapy followed by CS and salvage surgery, after dCRT or systemic immunochemotherapy. In this review, we will describe the latest developments in the multimodal treatment including chemotherapy, CRT, surgery, and immunotherapy, which may improve oncological and survival outcomes for patients with cT4 ESCC.

Renal function outcome after selective bladder-preserving tetramodality therapy consisting of maximal transurethral resection, induction chemoradiotherapy and consolidative partial cystectomy in comparison with radical cystectomy for patients with muscle-invasive bladder cancer: a two-centre retrospective study.

To compare renal function (RF) outcomes after bladder-preserving tetramodal therapy against muscle-invasive bladder cancer (MIBC) to those after radical cystectomy (RC). This study included 95 patients treated with tetramodal therapy consisting of transurethral bladder tumour resection, chemoradiotherapy and partial cystectomy (PC) and 300 patients treated with RC. The annual change in the estimated glomerular filtration rate (eGFR) was compared using the linear mixed model. Renal impairment was defined as a >25% decrease from the pretreatment eGFR, and renal impairment-free survival (RIFS) was calculated. The association between treatment type and renal impairment was assessed. The number of patients who received neoadjuvant chemotherapy was 8 (8.4%) in the tetramodal therapy group and 75 (25.0%) in the RC group. After the inverse probability of treatment weighting adjustments, the baseline characteristics were balanced between the treatment groups. The mean eGFR before treatment in tetramodal therapy and RC groups was 69.4 and 69.6 mL/min/1.73 m2 and declined with a slope of -0.7 and -1.5 mL/min/1.73 m2/year, respectively. The annual deterioration rate of post-treatment eGFR in the tetramodal therapy group was milder than in the RC group. The 5-year RIFS rate in the tetramodal therapy and the RC groups was 91.2 and 85.2%, respectively. Tetramodal therapy was an independent factor of better RIFS compared with RC. RF was better preserved after tetramodal therapy than after radical therapy; however, even after tetramodal therapy, the eGFR decreased, and a non-negligible proportion of patients developed renal impairment.

Prognostic impact of pathologically confirmed rib invasion in patients with lung cancer requiring chest wall resection.

Primary lung cancer that invades the chest wall is classified as T3 regardless of the depth of invasion. This study assessed the prognostic impact of pathologically confirmed rib invasion in patients with pT3N0-1 lung cancer requiring chest wall resection. We retrospectively analyzed the records of patients with non-small cell lung cancer (NSCLC) who underwent combined lung and chest wall resection with rib involvement from 2006 to 2019. The median follow-up period was 64.0 months. In total, 42 patients (41 men, 1 woman) were enrolled. The median patient age was 64 years (range, 42-79 years). The median tumor size before treatment was 56.5 mm (range, 21-80 mm), and an osteolytic sign was identified on computed tomography (CT) in 42.9% (18/42). Among 27 patients who received induction chemoradiotherapy, 5 (18.5%) achieved a complete pathological response. The operations comprised 36 lobectomies, 5 segmentectomies, and 1 wedge resection with resection of 2.5 ribs on average. Pathological examination revealed rib invasion in 18 (42.9%) patients. The 5-year disease-free and overall survival rates with pathological rib invasion were 44.4% and 77.4% (P=0.0114), respectively and those without pathological rib invasion were 44.7% and 81.3% (P=0.0222), respectively. Pathologically confirmed rib invasion was the only factor identified to have a prognostic impact in the univariate and multivariate analyses [hazard ratio (HR), 5.98; 95% confidence interval (CI): 1.37-26.1]. Locoregional recurrence and distant metastases were more common in patients with than without pathologically confirmed rib invasion [4 (22.2%) and 6 (33.3%), respectively, among 18 patients with pathological rib invasion; 2 (8.3%) and 3 (12.5%), respectively, among 24 patients without pathological rib invasion] (P=0.0073). Pathologically confirmed rib invasion was found to have a significant unfavorable prognostic impact in patients with pT3N0-1 lung cancer requiring chest wall resection. Multimodal therapy may be preferable in these patients to prevent local and distant relapse.

Spleen-preserving D2 subtotal distal resection of the stomach and corpocaudal resection of the pancreas after neoadjuvant induction chemotherapy and chemoradiotherapy: case report and literature review

Background. Stomach cancer is one of the most common cancers worldwide. Long-term treatment outcomes in patients with locally advanced gastric cancer with invasion to adjacent structures are poor. In clinical recommendations of the Ministry of Health of the Russian Federation, it is recommended to treat these patients with perioperative chemotherapy according to the FLOT scheme. The effectiveness of neoadjuvant chemoradiotherapy is studied in many multicenter studies involving randomized clinical trials. Case description. We present a case of a successful treatment of a patient with locally advanced gastric cancer (сT4bN2M0 – IVA stage). The patient received neoadjuvant therapy (2 cycles according to the FLOT scheme) followed by chemoradiotherapy (total dose of 46 Gy with the concurrent chemotherapy with capecitabine and oxaliplatin). Neoadjuvant therapy was well tolerated (grade 1 gastrointestinal and hematological toxicity). The patient underwent distal subtotal resection of the stomach with D2 lymph node dissection and distal subtotal resection of the pancreas with preservation of the spleen. No postoperative complications were observed. Histological examination revealed complete pathological response of the primary tumor, including the area of earlier invasion into the pancreas; metastasis in one lymph node of the small omentum. The patient is alive with no evidence of disease 20 months after surgery. Conclusion. The feasibility of conducting safe multimodal neoadjuvant therapy followed by organ-preserving surgery in a patient with locally advanced gastric cancer (сT4bN2M0) was shown. The effective neoadjuvant therapy resulted in the achievement of complete pathologic response, which is a favorable prognostic factor.

Radiothérapie et immunothérapie : avant, pendant ou après ?

Locally-advanced non-small cell lung cancer (NSCLC) stage III patients, represent one quarter of the whole NSCLC patients at diagnosis. Historical studies and the LACE meta-analysis showed the superiority of concurrent chemo-radiotherapy over sequential radiotherapy with a survival benefit of 5% at five years. The main advance in recent years has been the PACIFIC trial, which compared durvalumab with placebo for one year, after induction chemo-radiotherapy, in non-resectable stage III patients. Maintenance durvalumab survival advantage was obvious, with a median survival of 47.5 months in the experimental arm, compared to 29.1 months in the placebo arm (HR = 0.68), with a median follow-up exceeding 5 years, such survival benefit being absent in patients whose tumor had an oncogenic addictive mutation. Durvalumab association with other immune checkpoint inhibitors (anti CD73, anti NKG2A) appears promising in phase 2 trials, in such maintenance indication, phase 3 results being awaited. Feasibility of chemo-immunotherapy association with concurrent radiotherapy is currently assessed in many preliminary studies, with a specific focus on pulmonary safety. Neo-adjuvant immunotherapy before radio-chemotherapy is less extensively studied, with only fragmentary available data. The improvement or immunotherapy strategies, in association with chemo-radiotherapy in stage III non-resectable NSCLC patients, is thus possible in close future, even though PACIFIC trail results will be difficult to outperform.1877-1203/© 2022 SPLF. Published by Elsevier Masson SAS. All rights reserved.

A Dynamic Clinical Calculator for Estimating Conditional Recurrence-Free Survival After Total Neoadjuvant Therapy for Rectal Cancer and Either Surgery or Watch-and-Wait Management

The risk of recurrence in patients with locally advanced rectal cancer has historically been determined after surgery, relying on pathologic variables. A growing number of patients are being treated without surgery, and their risk of recurrence needs to be calculated differently. To develop a dynamic calculator for estimating the probability of recurrence-free survival (RFS) in patients with rectal cancer who undergo total neoadjuvant therapy (TNT) (induction systemic chemotherapy and chemoradiotherapy) and either surgery or watch-and-wait management. This cohort study included patients who presented with stage II or III rectal cancer between June 1, 2009, and March 1, 2015, at a comprehensive cancer center. Conditional modeling was incorporated into a previously validated clinical calculator to allow the probability of RFS to be updated based on whether the patient remained in watch-and-wait management or underwent delayed surgery. Data were analyzed from November 2021 to March 2022. TNT followed by immediate surgery or watch-and-wait management with the possibility of delayed surgery. RFS, concordance index, calibration curves. Of the 302 patients in the cohort, 204 (68%) underwent surgery within 3 months from TNT completion (median [range] age, 51 [22-82] years; 78 [38%] women), 54 (18%) underwent surgery more than 3 months from TNT completion (ie, delayed surgery; median [range] age, 62 [31-87] years; 30 [56%] female), and 44 (14%) remained in watch-and-wait management as of April 21, 2021 (median [range] age, 58 [32-89] years; 16 [36%] women). Among patients who initially opted for watch-and-wait management, migration to surgery due to regrowth or patient choice occurred mostly within the first year following completion of TNT, and RFS did not differ significantly whether surgery was performed 3.0 to 5.9 months (73%; 95% CI, 52%-92%) vs 6.0 to 11.9 months (71%; 95% CI, 51%-99%) vs more than 12.0 months (70%; 95% CI, 49%-100%) from TNT completion (P = .70). RFS for patients in the watch-and-wait cohort at 12 months from completion of TNT more closely resembled patients who had undergone surgery and had a pathologic complete response than the watch-and-wait cohort at 3 months from completion of TNT. Accordingly, model performance improved over time, and the concordance index increased from 0.62 (95% CI, 0.53-0.71) at 3 months after TNT to 0.66 (95% CI, 0-0.75) at 12 months. In this cohort study of patients with rectal cancer, the clinical calculator reliably estimated the likelihood of RFS for patients who underwent surgery immediately after TNT, patients who underwent delayed surgery after entering watch-and-wait management, and patients who remained in watch-and-wait management. Delayed surgery following attempted watch-and-wait did not appear to compromise oncologic outcomes. The risk calculator provided conditional survival estimates at any time during surveillance and could help physicians counsel patients with rectal cancer about the consequences of alternative treatment pathways and thereby support informed decisions that incorporate patients' preferences.

Mediastinal restaging with transcervical extended mediastinal lymphadenectomy in patients with locally advanced non-small cell lung cancer treated with pneumonectomy

Background: The purpose of this retrospective report was to assess long-term survival of patients with locally advanced non-small cell lung cancer (NSCLC) who underwent mediastinal restaging with transcervical extended mediastinal lymphadenectomy (TEMLA) after induction chemotherapy or chemoradiotherapy and then were treated with pneumonectomy.

Cost-effectiveness analysis of the new oncological drug durvalumab in Italian patients with stage III non-small cell lung cancer.

BackgroundThe monoclonal antibody durvalumab, an immune‐checkpoint inhibitor (ICI) antiprogrammed death ligand 1 (PD‐L1), is available for unresectable stage III NSCLC patients as consolidation therapy following induction chemoradiotherapy, with very promising overall survival (OS) and progression‐free survial (PFS) results in registration trials. The purpose of this study was to provide policymakers with an estimate of the cost‐effectiveness of durvalumab in the treatment of non‐small cell lung cancer (NSCLC).MethodsThe study developed a Markov model covering a 5‐year period to compare costs and outcomes of treating PD‐L1 positive patients with or without durvalumab. We conducted a series of sensitivity analyses (Tornado analysis and Monte Carlo simulation) by varying some parameters to assess the robustness of our model and identify the parameters with the greatest impact on cost‐effectiveness.ResultsPrior to the release of durvalumab, the management of NSCLC over a 5‐year period cost €33 317 per patient, with an average life expectancy of 2.01 years. After the introduction of the drug, this increased to €37 317 per patient, with an average life expectancy of 2.13 years. Treatment with durvalumab led to an incremental cost‐effectiveness ratio (ICER) of €35 526 per year. OS is the variable that contributes the most to the variability of the ICER.ConclusionsThe study observed that durvalumab is a cost‐effective treatment option for patients with unresectable stage III NSCLC.

Artificial reconstruction for a thymoma invading superior vena cava

Artificial reconstruction for a thymoma invading superior vena cava

Definitive chemoradiotherapy versus neoadjuvant chemoradiotherapy followed by surgery in patients with locally advanced esophageal squamous cell carcinoma who achieved clinical complete response when induction chemoradiation finished: A phase II random

Background and purposeMore than 40% of patients with esophageal squamous cell carcinoma (ESCC) exhibit pathological complete responses (pCR) after neoadjuvant chemoradiotherapy (nCRT), and theoretically, these patients may be cured by CRT and omit surgery. This prospectively randomized pilot study compared definitive chemoradiotherapy (dCRT) with nCRT in patients with locally advanced ESCC who achieved clinical complete responses (cCRs) to nCRT. Materials and methodsSingle center, randomized, open phase 2 study of 256 patients with locally advanced ESCC enrolled between April 2016 and November 2018. Immediately when nCRT finished, patients enrolled underwent response evaluations within 1 week. Patients with cCR were randomly allocated to undergo surgery (arm A) or complete CRT up to the definitive radiation dose (arm B). The primary end point was 3-year disease-free survival (DFS). ResultsFinally, 71 patients were randomly assigned to the nCRT (n = 36) and dCRT (n = 35) arms. The median observation time was 35.7 months. The 3-year DFS rate was 56.43 % in arm A versus 54.73 % in arm B (hazard ratio [HR] = 0.862, 95 % confidence interval [CI] = 0.452 to 1.645, P = 0.652). The 3-year overall survival (OS) rates in arms A and B were 69.5 % and 62.3 % (HR = 0.824, 95 % CI = 403–1.688, P = 0.597), respectively. ConclusionsAccording to our treatment response evaluation criteria, survival of the patients with cCR after nCRT was not significant different between nCRT group and dCRT group. An optimized response evaluation strategy soon after nCRT may guide next therapy decisions for patients with locally advanced ESCC.

Predictive factors of pathological complete response after induction (ypT0N0M0) in non-small cell lung cancer and short-term outcomes: Results of the Spanish Group of Video-assisted Thoracic Surgery (GE-VATS)

IntroductionTo analyze the predictors of pCR in NSCLC patients who underwent anatomical lung resection after induction therapy and to evaluate the postoperative results of these patients. MethodsAll patients prospectively registered in the database of the GE-VATS working group undergone anatomic lung resection by NSCLC after induction treatment and recruited between 12/20/2016 and 3/20/2018 were included in the study. The population was divided into two groups: patients who obtained a complete pathological response after induction (pCR) and patients who did not obtain a complete pathological response after induction (non-pCR). A multivariate analysis was performed using a binary logistic regression to determine the predictors of pCR and the postoperative results of patients were analyzed. ResultsOf the 241 patients analyzed, 36 patients (14.9%) achieved pCR. Predictive factors for pCR are male sex (OR: 2.814, 95% CI: 1.015−7.806), histology of squamous carcinoma (OR: 3.065, 95% CI: 1.233−7.619) or other than adenocarcinoma (OR: 5.788, 95% CI: 1.878−17.733) and induction therapy that includes radiation therapy (OR: 4.096, 95% CI: 1.785−9.401) and targeted therapies (OR: 7.625, 95% CI: 2.147−27.077). Prevalence of postoperative pulmonary complications was higher in patients treated with neoadjuvant chemo-radiotherapy (p = 0.032). ConclusionsMale sex, histology of squamous carcinoma or other than ADC, and induction therapy that includes radiotherapy or targeted therapy are positive predictors for obtaining pCR. Induction chemo-radiotherapy is associated with a higher risk of postoperative pulmonary complications.

Induction Chemotherapy and Chemoradiotherapy Combined to ASA vs. Placebo for High-Risk Rectal Cancer: Results of a Randomized Trial

Inductionchemotherapy (IC) followed by chemoradiation (CRT) is an attractive approach in high-risk locally advanced rectal cancer. Additionally, ASA has shown potential to improve outcomes alongside CRT in rectal cancer. The ICAR trial aimed to evaluate the safety and efficacy of IC followed by CRT with or without ASA on MRI tumor response. MethodsSingle-center, double-blind, randomized phase II trial to evaluate induction treatment with CAPOX, followed by capecitabine-based chemoradiotherapy with ASA (arm 1) or placebo (arm 2) in high-risk stage II-III rectal adenocarcinoma staged by MRI. The primary endpoint was MRI tumor regression grade (mrTRG). Secondary endpoints were pathological response, surgical outcomes, postoperative complications, treatment tolerance, DFS, and OS. ResultsBetween January 2018 and August 2019, 27 patients were eligible, 25 (92.5%) completed IC, and 23 patients were randomly assigned (12 to ASA group; 11 to placebo group). In the ASA arm, 3 pts (25%) presented distant disease progression at restaging. Seven patients (30.4%) had cCR after neoadjuvant treatment. All 13 patients submitted to surgery after neoadjuvant treatment underwent R0 resections except for 1 patient with positive CRM, and 12 patients (92.3%) had sphincter preservation. After a median follow-up of 34.9 months, the 2-year DFS was 83.1% and 3-year OS was 81.5%. ConclusionThere was good compliance in both treatment arms and encouraging cCR rate. ASA during CRT was safe but failed to improve on MRI tumor response. The study was closed due to the absence of benefits.

Role of fluorodeoxyglucose-positron emission tomography in predicting the pathological response and prognosis after neoadjuvant chemoradiotherapy for locally advanced non-small-cell lung cancer.

OBJECTIVESThe present study compared the utility of fluorodeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT) for predicting the pathological response and prognosis following neoadjuvant therapy for locally advanced non-small-cell lung cancer (NSCLC).METHODSThis retrospective analysis included 72 patients in whom adjacent structures showed involvement and/or cN2 NSCLC who received induction chemoradiotherapy (ICRT) and subsequent surgery at our hospital from 2008 to 2019. FDG-PET and CT were performed in all patients before and after ICRT using the same scanner with similar techniques. We calculated the reduction in the maximum standardized uptake value in FDG-PET (ΔSUVmax) and tumour size on CT (ΔCT-size) before and after ICRT and investigated the relationship between the pathological response and prognosis.RESULTSThe disease response was classified as a major pathological response in 43 patients, and a minor response in 29 patients. ΔSUVmax 60% and ΔCT-size 30% were identified as the optimal cut-off values for predicting a major pathological response. ΔSUVmax was superior to ΔCT-size in terms of sensitivity, specificity, positive predictive value and negative predictive value. Furthermore, ΔSUVmax was superior to ΔCT-size for predicting the prognosis.CONCLUSIONSBased on the results of the present study, FDG-PET appeared to have greater utility than CT in predicting the pathological response following ICRT and the postoperative prognosis in patients with locally advanced NSCLC.

Evolution of the Surgical Management of Lung Cancer Invading the Spine: A Single Center Experience.

For patients with locally advanced non-small cell lung cancer invading the spine, induction chemoradiotherapy combined with radical en bloc resection is the key to obtaining long-term survival. With time, our operative technique evolved to a two-step surgery as we experienced numerous perioperative complications during one step surgery. The aim of our study was to assess postoperative morbimortality and long-term survival of both techniques. We retrospectively reviewed all patients who underwent en bloc resection for lung cancer invading the spine between October 2012 and June 2020. Every patient underwent induction therapy. Sixteen patients were included: nine patients were operated on with one step surgery, seven patients were operated on with two step interventions. Twenty-five percent of patients had major perioperative complications and 56.2% of patients had major post-operative complications. Patients in the “one step” group tended to have more perioperative complications whereas patients in the “two step” group tended to have more post-operative complications. Overall 3-year survival was 40% in the one-step and 86% in the two-step surgery group. Although our practice has been improved by two-step interventions, post-operative morbidity remains significant. As long term survivals are encouraging, this type of treatment should still be proposed for highly selected patients, in specialized centers.

As time goes by–developments in surgery for esophageal cancer in the new millennium

Summary Background In the last two decades, both treatment options and epidemiological features of cancer have changed. We studied the influence of related parameters on the outcome of patients undergoing resection for esophageal carcinoma. Methods We analyzed 499 consecutive patients who underwent esophagectomy for carcinoma since January 2000, comparing 2000–2010 with 2011–2021 and examining changes over time. Results The percentage of men (87.9 vs. 86.9%; p = 0.74) in the two groups was unchanged, whereas mean age increased significantly from 60.8 to 65.2 years (p = 0.000). There was a trend towards an increase of adenocarcinoma (gamma = 0.120, ASE = 0.055). Despite significantly increasing use of induction chemoradiotherapy (p = 0.000) from 7.14% in 2000 to 68.9% in 2021 the distribution of pT, pN stage, grading and the rate of positive lateral resection margins remained unchanged. When comparing the two periods, the overall 30-day mortality was 4.4 vs. 4.2% (p = 0.56), recurrence-free survival was 36.9 vs. 38% at 60 months and 33.9 vs. 36.4% at 120 months (p = 0.93). Tumor-associated survival was 41.1 vs. 45% at 60 months and 35.5 vs. 38.7% at 120 months (p = 0.78). None of the survival rates differed significantly. A multivariable analysis of year of surgery, age, sex, histological subtype, grading, pT, pN, lateral resection margin, and induction therapy showed that only higher pT (p = 0.01), positive pN (p = 0.000), positive lateral margin (p = 0.003), squamous cell carcinoma (p = 0.04) and higher grading (p = 0.026) had a statistically significant, independent, negative influence on prognosis. Conclusion Optimized noninvasive and invasive therapeutic modalities have produced only marginal improvement in the prognosis of esophageal cancer within the last two decades.

Final results of the IFCT-0803 study, a phase II study of cetuximab, pemetrexed, cisplatin, and concurrent radiotherapy in patients with locally advanced, unresectable, stage III, non-squamous, non-small-cell lung cancer

PurposeRoughly 20% of patients with non-small-cell lung cancer exhibit locally advanced, unresectable, stage III disease. Concurrent platinum-based chemoradiotherapy is the backbone treatment, which is followed by maintenance immunotherapy, yet with poor long-term prognosis. This phase II trial (IFCT-0803) sought to evaluate whether adding cetuximab to cisplatin and pemetrexed chemoradiotherapy would improve its efficacy in these patients. Materials and methodsEligible patients received weekly cetuximab (loading dose 400mg/m2 day 1; subsequent weekly 250mg/m2 doses until two weeks postradiotherapy). Chemotherapy comprised cisplatin (75mg/m2) and pemetrexed (500mg/m2), both delivered on day 1 of a 21-day cycle of maximally four. Irradiation with maximally 66Gy started on day 22. Disease control rate at week 16 was the primary endpoint. ResultsOne hundred and six patients were included (99 eligible patients). Compliance exceeded 95% for day 1 of chemotherapy cycles 1 to 4, with 76% patients receiving the 12 planned cetuximab doses. Maximal grade 3 toxicity occurred in 63% patients, and maximal grade 4 in 9.6%. The primary endpoint involving the first 95 eligible patients comprised two (2.1%) complete responses, 57 (60.0%) partial responses, and 27 (28.4%) stable diseases. This 90.5% disease control rate (95% confidence interval [95% CI]: 84.6%–96.4%) was achieved at week 16. After median 63.0-month follow-up, one-year and two-year survival rates were 75.8% and 59.5%. Median overall survival was 35.8months (95% CI: 23.5–NR), and median progression-free survival 14.4months (95% CI: 11.2–18.8), with one-year and two-year progression-free survival rates of 57.6% and 34.3%. ConclusionThese survival rates compare favourably with published data, thus justifying further development of cetuximab-based induction chemoradiotherapy.

Patterns and influence of nodal metastases after neoadjuvant chemoradiation and R0 resection in esophageal adenocarcinoma

ObjectiveLittle is known about the pattern of nodal metastases in patients with esophageal adenocarcinoma who have received neoadjuvant chemoradiation and undergone surgery. We sought to assess this pattern and evaluate its association with prognosis. MethodsAll patients with esophageal adenocarcinoma who underwent neoadjuvant chemoradiation and R0 esophagectomy between 2010 and 2018 at our institution were included (n = 537). The primary objective was to evaluate the association of sites of lymph node metastases with disease-free survival. The number of nodal stations and individual sites of nodal metastases were evaluated first in univariable then in separate multivariable Cox regression models adjusted for clinical factors. ResultsOf 537 patients, 193 (36%) had pathologic nodal metastases at the time of surgery; 153 (28%) had single-station disease, 32 (6.0%) had 2-station disease, and 8 (1.5%) had 3-station disease. The majority of patients with multiple positive nodal stations had positive nodes in the paraesophageal (93%) and/or left gastric stations (60%). Multivariable models controlling for clinical factors showed that an increasing number of positive nodal stations (hazard ratio, 1.59; 95% CI, 1.35-1.84; P < .01)—in particular, the subcarinal (hazard ratio, 2.78; 95% CI, 1.54-5.03; P < .01) and paraesophageal stations (hazard ratio, 2.0; 95% CI, 1.58-2.54; P < .01)—was associated with increased risk of recurrence. ConclusionsOne-third of patients who have undergone R0 resection for esophageal adenocarcinoma following induction chemoradiation therapy have metastatic lymph nodes. An increasing number of nodal stations, particularly paraesophageal and subcarinal metastases, were associated with increased risk of recurrence.