Use Of Perioperative Chemotherapy Research Articles

Evaluating the Survival Benefits of Perioperative Chemotherapy in Frail and Morbid Muscle-Invasive Bladder Cancer Patients.

Current guidelines endorse the use of perioperative chemotherapy (POC) in muscle-invasive bladder cancer (MIBC) to enhance the long-term overall survival (OS) compared to radical cystectomy (RC) alone. This study aims to assess the impact of POC on the OS in frail and morbid (F-M) patients undergoing RC. A retrospective multicenter study of 291 patients who underwent RC between 2015 and 2019 was performed. Patients with both a Charlson comorbidity index ≥ 4 and Modified Frailty Index ≥ 2 were classified as the F-M cohort. We compared the clinical and pathological characteristics and outcomes of the F-M patients who received POC to those who underwent RC alone. Univariable and multivariable analyses were performed to identify the predictors of the OS. The F-M cohort included 102 patients. POC was administered to 44% of these patients: neoadjuvant (NAC) to 31%, adjuvant (AC) to 19%, and both to 6 (6%). The OS was significantly lower in the F-M cohort compared to in the healthier patients (median OS 42 months, p = 0.02). The F-M patients who received POC were younger, less morbid and had better renal function. Although POC was marginally associated with improved OS in the univariable analysis (p = 0.06), this was not significant in the multivariable analysis (p = 0.50). NAC was associated with improved OS in the univariable analysis (p = 0.004) but not after adjustment for competing factors (p = 1.00). AC was not associated with the OS. POC does not improve the OS in F-M patients undergoing RC. Personalized treatment strategies and further prospective studies are needed to optimize care in this unique vulnerable population.

Has Management of Intrahepatic Cholangiocarcinoma Evolved with the Evidence? Trends and Practice Patterns from the National Cancer Database.

Management of intrahepatic cholangiocarcinoma (IHC) has advanced in recent decades, including randomized trial evidence supporting systemic therapy in the palliative and adjuvant setting. Mounting observational evidence suggests resection of IHC with multifocal disease (IHC-MF) or lymph node metastasis (IHC-LNM) should be limited. It is unknown how real-world practice has evolved in light of research advances. This study characterizes trends in management and outcomes of IHC without distant metastasis. We queried the National Cancer Database (NCDB) for patients treated for IHC without distant metastasis (M0) and identified subgroups with lymph node (cN1) or multifocal hepatic involvement (cT2b). Two-sided Cochran-Armitage tests evaluated trends in initial treating modality and perioperative chemotherapy. Logistic regression evaluated associations with choice of initial treating modality. Overall survival (OS) was evaluated by using Kaplan-Meier methods. Between 2004 and 2020, 11,368 patients were treated for IHC without extrahepatic metastasis. Forty-three percent underwent resection. Initial management shifted from resection towards radiation or systemic therapy in IHC-MF and IHC-LNM. Use of perioperative chemotherapy increased from 39% pre-2010 to 70% in 2018-2020 (p < 0.001), most often delivered postoperatively. Across the entire cohort, median OS improved from 16 (95% confidence interval [CI] 15-18) to 27 months (95% CI 26-29). More modest improvements were observed in IHC-MF and IHC-LNM. Use of perioperative chemotherapy has been widely adopted, predating randomized trial evidence in the adjuvant setting. Initial management of IHC-MF and IHC-LNM has shifted from resection to systemic and/or radiation therapy. While OS has improved overall, outcomes of IHC-MF and IHC-LNM remain poor, warranting further investigation.

What Is the Impact of Multimodal Treatment in Patients with Leiomyosarcoma of Bone? A Multicenter Study of 35 Patients with an Ultra-Rare Tumor Entity.

Primary leiomyosarcoma of bone (LMSoB) is extremely rare, comprising only <0.7% of primary malignant bone tumors, and is therefore considered an ultra-rare tumor entity. There is currently no consensus as to whether therapeutic strategies should be based on the biological characteristics of soft tissue leiomyosarcoma or on primary tumor localization in the bone. The use of perioperative chemotherapy and its effectiveness in this rare tumor entity remains unclear. We aimed to evaluate the impact of different treatment approaches in a multicenter setting with a total of 35 patients included. The 5-year overall survival (OS) was 74%. Patients with localized disease undergoing surgery had a significantly higher 5-year OS compared to patients who did not undergo surgical treatment (82% vs. 0%, p = 0.0015). Axial tumor localization was associated with worse event-free survival (EFS) probability (p < 0.001) and OS (p = 0.0082). A high proportion of our patients developed secondary metastases. Furthermore, the perioperative chemotherapy protocols applied to our patients were not associated with an improved EFS or OS. Therefore, the benefit of perioperative chemotherapy in LMSoB needs to be further investigated, and the choice of agents still needs to be clarified.

Neoadjuvant chemoimmunotherapy in locally advanced gastric or gastroesophageal junction adenocarcinoma.

Patients suffering from locally advanced gastric or gastroesophageal junction adenocarcinoma often face a high postoperative recurrence rate. Despite aggressive treatment, less than 50% survive beyond five years. Ongoing clinical studies are exploring ways to prolong patient survival, revealing that perioperative chemotherapy can extend both the period of recurrence-free survival and overall survival for this group of patients. Currently, combining chemotherapy and immune checkpoint inhibitors has become a critical treatment approach for advanced gastric or gastroesophageal junction adenocarcinoma. However, the effectiveness of this approach in locally advanced patients remains unverified. This article delves into the latest research concerning the use of perioperative chemotherapy coupled with immune checkpoint inhibitors in locally advanced gastric or gastroesophageal junction adenocarcinoma treatment, and highlights prospective challenges and discusses how to best identify patients who may benefit from combined chemotherapy and immune checkpoint inhibitor therapy.

Implementation of Best Practices in Pancreatic Cancer Care in the Netherlands: A Stepped-Wedge Randomized Clinical Trial.

Implementation of new cancer treatment strategies as recommended by evidence-based guidelines is often slow and suboptimal. To improve the implementation of guideline-based best practices in the Netherlands in pancreatic cancer care and assess the impact on survival. This multicenter, stepped-wedge cluster randomized trial compared enhanced implementation of best practices with usual care in consecutive patients with all stages of pancreatic cancer. It took place from May 22, 2018 through July 9, 2020. Data were analyzed from April 1, 2022, through February 1, 2023. It included all patients in the Netherlands with pathologically or clinically diagnosed pancreatic ductal adenocarcinoma. This study reports 1-year follow-up (or shorter in case of deceased patients). The 5 best practices included optimal use of perioperative chemotherapy, palliative chemotherapy, pancreatic enzyme replacement therapy (PERT), referral to a dietician, and use of metal stents in patients with biliary obstruction. A 6-week implementation period was completed, in a randomized order, in all 17 Dutch networks for pancreatic cancer care. The primary outcome was 1-year survival. Secondary outcomes included adherence to best practices and quality of life (European Organisation for Research and Treatment of Cancer [EORTC] global health score). Overall, 5887 patients with pancreatic cancer (median age, 72.0 [IQR, 64.0-79.0] years; 50% female) were enrolled, 2641 before and 2939 after implementation of best practices (307 during wash-in period). One-year survival was 24% vs 23% (hazard ratio, 0.98, 95% CI, 0.88-1.08). There was no difference in the use of neoadjuvant chemotherapy (11% vs 11%), adjuvant chemotherapy (48% vs 51%), and referral to a dietician (59% vs 63%), while the use of palliative chemotherapy (24% vs 30%; odds ratio [OR], 1.38; 95% CI, 1.10-1.74), PERT (34% vs 45%; OR, 1.64; 95% CI, 1.28-2.11), and metal biliary stents increased (74% vs 83%; OR, 1.78; 95% CI, 1.13-2.80). The EORTC global health score did not improve (area under the curve, 43.9 vs 42.8; median difference, -1.09, 95% CI, -3.05 to 0.94). In this randomized clinical trial, implementation of 5 best practices in pancreatic cancer care did not improve 1-year survival and quality of life. The finding that most patients received no tumor-directed treatment paired with the poor survival highlights the need for more personalized treatment options. ClinicalTrials.gov Identifier: NCT03513705.

Clinico-pathological Outcomes of Muscle Invasive Carcinoma Bladder in Post Neoadjuvant Chemotherapy Radical Cystectomy

Background: Neoadjuvant chemotherapy (NAC) before radical cystectomy is advocated in patients with muscle invasive urothelial carcinoma of the bladder with the goal to improve survival by downstaging the primary tumour and eradicating micro-metastasis. The use of perioperative chemotherapy for bladder cancer, particularly in the neoadjuvant setting, remains limited. This study was designed to evaluate NAC plus RC regarding pathological response, perioperative morbidity and mortality outcomes. Methods: This is a prospective and retro prospective study that was carried out from Jan 2018 to Jan 2020 for patients with muscle invasive bladder carcinoma. All patients having operable muscle invasive bladder carcinoma, Eastern Cooperative Oncology Group (ECOG) performance status 0–1 were included. Patients found to have metastatic disease, recurrent disease, patient not able to tolerate NAC were excluded from the study. Results: Early complications occurred within 30 days after surgery &amp; pathological response rates, perioperative morbidity, and mortality were compared. Conclusions: A short course of neoadjuvant chemotherapy was associated to a low incidence of serious adverse events and did not increase the post-operative morbidity. Results suggest that non-urothelial tumour showed no response to Platinum based combination chemotherapeutic regimens. After NAC, residual local disease, persistent nodal disease and status of surgical margins are the most powerful prognostic factors for patients who underwent RC.

Actualización en cáncer gástrico

Gastric cancer (GC) is the second most common gastrointestinal neoplasm. Despite a declining incidence in recent years, it is the third leading cause of death due to cancer in the world. Histologically, the most frequent GC is adenocarcinoma. It is related to multiple factors, including Helicobacter pylori infection, atrophic gastritis, and pernicious anemia. Symptoms of the disease appear in advanced stages and are nonspecific, which contributes to a late diagnosis. An upper gastrointestinal endoscopy with biopsy collection is the diagnostic method of choice and the first test to be performed when GC is suspected. The extension study should be performed using other tests, such as computed tomography (CT), echoendoscopy, or positron emission tomography combined with CT. Surgical resection with a lymphadenectomy is the mainstay of curative treatment in the absence of metastatic disease; increased survival has been demonstrated when it is combined with the use of perioperative chemotherapy. Endoscopic resection techniques such as mucosal resection and, mainly, submucosal dissection can be curative in select cases of early gastric cancer.

Has management of locally advanced intrahepatic cholangiocarcinoma evolved with the evidence? Trends and practice patterns from the National Cancer Database.

464 Background: Intrahepatic cholangiocarcinoma (IHC) is often advanced at presentation. Mounting evidence suggests a limited role for surgical resection in the setting of multifocal hepatic and regional lymph node involvement in favor of initial treatment with systemic therapy. We sought to characterize trends and practice patterns in the management of patients with locally advanced IHC without distant extrahepatic metastasis. Methods: We queried the National Cancer Database (NCDB) for patients with IHC between 2004-2020. Patients with inadequate data quality, carcinoma in situ, other primary cancers prior to IHC diagnosis, distant metastasis (M1), unknown M status (MX), and no treatment were excluded. Lymph node involvement was categorized using clinical N stage to reflect clinical decision-making. Due to AJCC staging updates and coding limitations, subgroup analysis of patients with multifocal disease (T2bNXM0 in the 7th AJCC edition) was confined to 2010-2017. A two-sided Cochran-Armitage test was used to evaluate time trends and Kaplan Meier methods were used to summarize overall survival (OS). Results: Of 11,368 patients treated for IHC without distant metastasis between 2004-2020, 2,467 / 10,183 (24%) with clinical lymph node staging had positive nodes; the subgroup with multifocal disease comprised 1,384 patients staged T2bNXM0 between 2010-2017. Overall, 36% of patients received formal resection as first treating modality and 59% received systemic or radiation therapy first. The use of perioperative chemotherapy in combination with formal resection increased from 39% pre 2010 to 70% in 2018-2020 (p&lt;0.001), most often delivered post-operatively: 49% received adjuvant, 13% neoadjuvant, and 8% both in 2018-2020. Among those with clinically positive lymph nodes, there was a decreasing trend in upfront resection (p&lt;0.001) and an increase in systemic or radiation therapy first (p&lt;0.001). Similarly, in the multifocal disease subgroup analysis, the proportion of upfront formal resection trended down from 33% in 2010 to 12% in 2017 (p&lt;0.001). Across the entire cohort, median OS improved from 16 months (IQR 15, 18) to 27 months (IQR 26, 29) for patients diagnosed 2018-2019 compared to &lt;2010. Conclusions: Over the last decade, increasing evidence has demonstrated unfavorable outcomes of surgical resection in locally advanced IHC even without distant extrahepatic disease, and supported the use of multimodality therapy. The most significant overall trends have been increasing use of perioperative systemic therapy in combination with formal resection compared to resection alone and an improvement in overall survival. On subgroup analysis, there was a significant and appropriate trend away from resection as first treatment modality for patients with clinically positive lymph nodes or multifocal disease.

Effectiveness of perioperative chemotherapy and radical cystectomy in treating bladder cancer

BackgroundDespite abundant evidence supporting the use of perioperative chemotherapy from clinical trials, no study to date has comprehensively evaluated its use in the treatment of muscle-invasive bladder cancer (MIBC) in the real-world setting. Little is known regarding the impact of pretreatment disease stage and real-world factors such as patient comorbidities preventing timely completion of therapy on its effectiveness. This study aims to assess the usage of perioperative chemotherapy and examines its impact on pathologic downstaging rates and recurrence free survival in patients undergoing radical cystectomy. MethodsA retrospective review was conducted in 805 patients with muscle invasive bladder cancer undergoing radical cystectomy with no perioperative chemotherapy, 761 with presurgical chemotherapy followed by radical cystectomy, and 134 radical cystectomy followed by adjuvant chemotherapy. Relevant clinicopathologic features were reviewed. Recurrence-free survival and Overall Survival probability estimates were calculated using the Kaplan–Meier method and compared using the Log-rank or Gehan-Breslow tests. The prognostic effects of presurgical chemotherapy and adjuvant chemotherapy regimens were evaluated by estimating hazard ratio and 95% confidence interval from an adjusted Cox proportional hazards model. Statistical tests were 2-sided, and significance was defined as P-value < 0.05. ResultsIn this contemporary, real-world cohort, 5-yr RFS was found to be 65.6% in pT0, 59.1%in <pT2, 35.4% in pT2, 15.3% in >pT2, and 10.8% in pN+ patients. Presurgical chemotherapy increased pathologic downstaging rates from 27.5% to 41.1% in patients with ≥cT2 BCa. Stratified by clinical T-stage, only cT2 patients derived recurrence-free survival (Median 45.3 months vs. 29.0 months, P < 0.01) and overall survival (Median 62.3 months vs. 41.9 months, P < 0.001) benefits. In patients with adverse pathologic features (≥pT3 or pN+), adjuvant chemotherapy improved recurrence-free survival (Median 22.8 months vs. 10.0 months, P < 0.0001) and overall survival (Median OS 32.4 months vs. 16.3 months, P < 0.0001). ConclusionsWe report real-world outcomes from a large cohort of muscle-invasive bladder cancer patients undergoing surgical treatment with/out perioperative chemotherapy. Pathologic response rates to pre-surgical chemotherapy were modest and led to clinical benefit only in cT2 patients. Adjuvant chemotherapy provided survival benefit for pathologically advanced MIBC patients irrespective of pT/N staging.

Nationwide implementation of best practices in pancreatic cancer care (PACAP-1): Stepped-wedge cluster randomized trial.

4152 Background: Implementation of new treatment strategies in cancer care is often inadequate and slow. We aimed to implement best practices in pancreatic cancer care using a nationwide stepped wedge design and assess the impact on overall survival. Methods: Nationwide multicenter stepped-wedge cluster randomized controlled trial comparing implementation of best practices with usual care (May 22, 2018 – May 29, 2020). Best practices included adequate use of perioperative and palliative chemotherapy, pancreatic enzyme replacement therapy (PERT), and metal biliary stents. The 6-week implementation period in all 17 Dutch pancreatic centers and their regional referral networks included monitoring, return visits, and provider feedback in combination with education and reminders. Primary outcome was one-year overall survival for all disease stages and secondary outcomes included guideline compliance and quality of life. Results: Overall, 5580 patients diagnosed with pancreatic cancer were included; 2939 after implementation of best practices versus 2641 before. One-year survival did not differ among the groups (HR 0.98, 95 CI 0.88-1.08). Overall use of perioperative chemotherapy (neoadjuvant and adjuvant) did not significantly differ, but use of palliative chemotherapy significantly increased (23.9% to 30.3%, OR 1.38, 95 CI 1.10-1.74). Also the use of PERT (34.2% to 45.2%, OR 1.64, 95 CI 1.28-2.11); and metal biliary stents (74.1.% to 83.3%, OR 1.78, 95 CI 1.13-2.08) significantly increased. The Global Health Score did not differ (AUC 43.8 to 42.7, median difference -1.12, 95 CI -3.13-0.80, n=655). Conclusions: This nationwide population-based trial to enhance implementation of best practices in pancreatic cancer care showed successful implementation of most best practices, but no increase in one-year survival and quality of life. Clinical trial information: NCT03513705 .

Wound complications in metastatic spine tumor patients with and without preoperative radiation.

Wound complications are a common adverse event following metastatic spine tumor surgery. Some patients with spinal metastases may first undergo radiation but eventually require spinal surgery because of either cord compression or instability. The authors compared wound complication rates in patients who had undergone surgery for metastatic disease and received preoperative radiation treatments, postoperative radiation, or no radiation. Records from patients treated at the University of California, San Francisco, for metastatic spine disease between 2005 and 2017 were retrospectively reviewed. Baseline characteristics were collected, including preoperative Karnofsky Performance Status (KPS), Spine Instability Neoplastic Score, total radiation dose, indication for surgery, diabetes status, time between radiation and surgery, use of perioperative chemotherapy or steroids, estimated blood loss, extent of fusion, and preoperative albumin level. Wound complication was defined as poor healing, dehiscence, or infection per the Centers for Disease Control and Prevention guidelines, within 6 months of surgery. One-way ANOVA was used to compare means across groups. Cumulative incidence analysis with competing risk methodology was used to adjust for risk of death during follow-up. Statistical analysis was performed using R software. Two hundred five patients with adequate medical records were identified. Seventy patients had received preoperative radiation, 74 had received postoperative radiation within 6 months after surgery, and 61 had received no radiation at the surgical site. Wound complication rates were similar across the 3 cohorts: 14.3% (n = 10) in the group with preoperative radiation, 10.8% (n = 8) in the group that received postoperative radiation, and 11.5% (n = 7) in the group with no radiation (p = 0.773). Competing risk analysis showed a higher cumulative incidence of wound complications for the preoperative cohort, though this difference was not significant (p = 0.46). Overall, 89 patients were treated with external beam radiation therapy (EBRT), whereas 55 received stereotactic body radiation therapy (SBRT). There was no significant difference in wound complications for patients treated with EBRT (11.2%, n = 10) versus SBRT (14.5%, n = 8; p = 0.825). KPS was the only factor correlated with wound complications on univariate analysis (p = 0.03). Wound complication rates did not differ across the 3 cohorts: patients treated with preoperative radiation, postoperative radiation within 6 months of surgery, or no radiation. The effect size was small for KPS and likely does not represent a clinically significant predictor of wound complications.

Appendiceal goblet cell carcinoma has marginal advantages from perioperative chemotherapy: a population-based study with an entropy balancing analysis

PurposeThe aim is to clarify the use of perioperative chemotherapy in resectable goblet cell carcinoma (GCC).MethodsA retrospective study was carried out based on the Surveillance, Epidemiology, and End Results study. The population was divided: into patients who received only radical surgery (group A) and those who received radical surgery plus chemotherapy (group B). An entropy balancing was carried out to correct the imbalance between the two groups. Two models were generated. Model 1 contained only high-risk patients: group B and a “virtual” group A with similar characteristics. Model 2 included only low-risk patients: group A and “virtual” group B with identical attributes. The efficacy of entropy balancing was evaluated with the d value. The overall survival was compared and reported with Hazard Ratio (HR) within a confidence interval of 95% (95 CI).ResultsThe groups A and B were imbalanced for tumor size (d = 0.392), T (d = 1.128), N (d = 1.340), M (d = 1.456), mean number of positive lymph nodes (d = 0.907), and LNR (d = 0.889). Before the balancing, the risk of death was higher in group B than in A (4.3; 2.5 to 7.4). After reweighting, all large differences were eliminated (d < 0.200). In high-risk patients, the risk of death was higher in patients who underwent surgery alone than those who received perioperative chemotherapy (HR 0.5; 0.2 to 1.3) without statistical significance (p = 0.187). In low-risk patients, the risk of death was similar (HR 1.1; 0.3 to 3.3).ConclusionPerioperative chemotherapy could provide some marginal advantages to high-risk patients.

Prognostic Value of Pre-Treatment [18F]FDG PET/CT Texture Analysis in Undifferentiated Soft-Tissue Sarcoma

Undifferentiated soft-tissue sarcomas (USTS) are one of the most common sarcoma histotypes in adults. The standard of care is surgical excision plus adjuvant radiotherapy, while the use of perioperative chemotherapy is still controversial. The aim of this study was to investigate the value of pre-treatment [18F]FDG PET/CT conventional metrics and textural features in predicting disease-free survival (DFS) and overall survival (OS) in patients with USTS of the limbs and trunk. [18F]FDG PET/CT scans of 51 consecutive patients with locally advanced USTS were retrospectively evaluated. Conventional and textural PET parameters were analysed and tested as predictive factors for DFS and OS. During a median follow up of 50.7 months, 23 (45.1%) and 29 (56.9%) patients had death or disease progression, respectively. Univariate analysis revealed a significant association for perioperative treatment, PET volumetric parameters and the textural feature GLCM_correlation with DFS and OS. In multivariate analysis, perioperative treatment and GLCM_correlation were the only independent factors, allowing stratification of the population into three different prognostic classes. GLCM_correlation can identify USTS at high risk of relapse and death, thus helping to optimize the perioperative treatment of patients.

Localized gastric mesothelioma with nodal metastasis-an exceptionally rare entity.

Localized mesothelioma is a rare disease with very few reports of presentation in visceral organs. We report a case of localized gastric mesothelioma with lymph node metastasis in a 32-year-old man without asbestos exposure. A failed attempt at resection was made before presentation at another center. He was given perioperative chemotherapy that was followed by a D2 radical subtotal gastrectomy and hyperthermic intraperitoneal chemotherapy. Histopathology showed epithelioid mesothelioma with nodal metastasis but without visceral peritoneal involvement. Cytoreductive surgery and regional chemotherapy are standard in diffuse mesothelioma. Management of localized mesothelioma is anecdotal; however aggressive surgery plays a central role with selective use of perioperative chemotherapy.

Neoadjuvant Treatment Strategies for Resectable Proximal Gastric, Gastroesophageal Junction and Distal Esophageal Cancer.

Simple SummaryThe five-year survival for resectable proximal gastric, gastroesophageal junction (GEJ), and distal esophageal cancer ranges from 30 to 60% globally. Neoadjuvant and/or perioperative therapy has emerged as a treatment tool to improve patient selection for surgery, resectability, and locoregional control of the disease. As a result, treatment strategies have evolved from the first trials in the late 1980s to the pivotal CROSS trial updated in 2015. The review summarizes current clinical trials and treatment recommendations with regard to neoadjuvant and/or perioperative therapy for patients with adenocarcinoma and squamous cell carcinoma of the distal esophagus, GEJ, and proximal stomach.Neoadjuvant treatment strategies for resectable proximal gastric, gastroesophageal junction (GEJ), and distal esophageal cancer have evolved over several decades. Treatment recommendations differ based on histologic type—squamous cell carcinoma (SCC) versus adenocarcinoma (AC)—as well as the exact location of the tumor. Recent and older clinical trials in this area were critically reviewed. Neoadjuvant chemoradiation with concurrent taxane- or fluoropyrimidine-based chemotherapy has an established role for both AC and SCC of the distal esophagus and GEJ. The use of perioperative chemotherapy for gastric AC is based on the FLOT4 and MAGIC trials; however, the utility of neoadjuvant chemoradiation in this setting requires further evaluation. Additional clinical trials evaluating chemotherapy, targeted therapy, immunotherapy, and radiation that are currently in process are highlighted, given the need for further disease control.

Focused versus conventional radiotherapy in spinal oncology: is there any difference in fusion rates and pseudoarthrosis?

Radiotherapy is considered standard of care for adjuvant peri-operative treatment of many spinal tumors, including those with instrumented fusion. Unfortunately, radiation treatment has been linked to increased risk of pseudoarthrosis. Newer focused radiotherapy strategies with enhanced conformality could offer improved fusion rates for these patients, but this has not been confirmed. We performed a retrospective analysis of patients at three tertiary care academic institutions with primary and secondary spinal malignancies that underwent resection, instrumented fusion, and peri-operative radiotherapy. Two board certified neuro-radiologists used the Lenke fusion score to grade fusion status at 6 and 12-months after surgery. Secondary outcomes included clinical pseudoarthrosis, wound complications, the effect of radiation timingand radiobiological dose delivered, the use of photons versus protons, tumor type, tumor location, and use of autograft on fusion outcomes. After review of 1252 spinal tumor patients, there were 60 patients with at least 6months follow-up that were included in our analyses. Twenty-five of these patients received focused radiotherapy, 20 patients received conventional radiotherapy, and 15 patients were treated with protons. There was no significant difference between the groups for covariates such as smoking status, obesity, diabetes, intraoperative use of autograft, and use of peri-operative chemotherapy. There was a significantly higher rate of fusion for patients treated with focused radiotherapy compared to those treated with conventional radiotherapy at 6-months (64.0% versus 30.0%, Odds ratio: 4.15, p = 0.036) and 12-months (80.0% versus 42.1%, OR: 5.50, p = 0.022). There was a significantly higher rate of clinical pseudoarthrosis in the conventional radiotherapy cohort compared to patients in the focused radiotherapy cohort (19.1% versus 0%, p = 0.037). There was no difference in fusion outcomes for any of the secondary outcomes except for use of autograft. The use of intra-operative autograft was associated with an improved fusion at 12-months (66.7% versus 37.5%, OR: 3.33, p = 0.043). Focused radiotherapy may be associated with an improved rate of fusion and clinical pseudoarthrosis when compared to conventional radiation delivery strategies in patients with spinal tumors. Use of autograft at the time of surgery may be associated with improved 12-month fusion rates. Further large-scale prospective and randomized controlled studies are needed to better stratify the effects of radiation delivery modality in these patients.

Nutritional Support Indications in Gastroesophageal Cancer Patients: From Perioperative to Palliative Systemic Therapy. A Comprehensive Review of the Last Decade.

Gastric cancer treatments are rapidly evolving, leading to significant survival benefit. Recent evidence provided by clinical trials strongly encouraged the use of perioperative chemotherapy as standard treatment for the localized disease, whereas in the advanced disease setting, molecular characterization has improved patients’ selection for tailored therapeutic approaches, including molecular targeted therapy and immunotherapy. The role of nutritional therapy is widely recognized, with oncologic treatment’s tolerance and response being better in well-nourished patients. In this review, literature data on strategies or nutritional interventions will be critically examined, with particular regard to different treatment phases (perioperative, metastatic, and palliative settings), with the aim to draw practical indications for an adequate nutritional support of gastric cancer patients and provide an insight on future directions in nutritional strategies. We extensively analyzed the last 10 years of literature, in order to provide evidence that may fit current clinical practice both in terms of nutritional interventions and oncological treatment. Overall, 137 works were selected: 34 Randomized Clinical Trials (RCTs), 12 meta-analysis, 9 reviews, and the most relevant prospective, retrospective and cross-sectional studies in this setting. Eleven ongoing trials have been selected from clinicaltrial.gov as representative of current research. One limitation of our work lies in the heterogeneity of the described studies, in terms of sample size, study procedures, and both nutritional and clinical outcomes. Indeed, to date, there are no specific evidence-based guidelines in this fields, therefore we proposed a clinical algorithm with the aim to indicate an appropriate nutritional strategy for gastric cancer patients.

Impact of perioperative chemotherapy on postoperative morbidity after gastrectomy for gastric cancer

IntroductionThe use of perioperative chemotherapy (CT) in patients with advanced gastric carcinoma increases their overall survival. This therapy may also increase the number of patients with R0 resection. Potential drawbacks of this therapy, besides its toxicity, include increased surgical morbidity. MethodsWe retrospectively evaluated the records of patients undergoing gastrectomy with curative intent, for carcinoma, at our institution between January 2009 and August 2018. They were divided into two groups: direct surgery (SURG) and perioperative CT (CHEMO). Patients with other neoadjuvant therapies and cardia Siewert I and II carcinomas were excluded.The primary objective was to evaluate the impact of perioperative CT on surgical morbidity. As secondary objectives, resection radicality and total lymph node count were compared between the two groups. ResultsA total of 307 patients (97 direct surgery and 210 perioperative CT) were evaluated. Median age was 67 years old.The overall major surgical morbidity (Clavien-Dindo 3–5) was 10.6% in the CHEMO group and 12.4 in the SURG group (p=0.643).There was no statistically significant difference between the surgical radicality (R0 98% in the SURG group vs 97.5% CHEMO group (p=0.865). There was an increase in the total number of lymph nodes retrieved in the specimen in the CHEMO group (25 vs 22, p=0.001), a difference that was not maintained in the subgroup analysis as a function of the surgery performed. ConclusionsPerioperative CT in gastric carcinoma does not increase surgical morbidity, surgical radicality and total lymph node count.

Patterns of Perioperative Treatment and Survival of Localized, Resected, Intermediate- or High-Grade Soft Tissue Sarcoma: A 2000-2017 Netherlands Cancer Registry Database Analysis.

Background Standard therapy for localized soft tissue sarcoma (STS) is wide, limb-sparing resection. For intermediate- or high-grade tumors, (neo)adjuvant therapies are frequently added to the treatment plan. In this study, data from a Dutch nationwide database are used to (1) assess whether perioperative management of STS follows ESMO guidelines, (2) characterize prognostic factors for overall survival (OS), and (3) assess the association between perioperative treatment and survival. Methods All intermediate- or high-grade, localized STS cases, who have undergone surgery and diagnosed between 2000 and 2017, were identified in the Netherlands Cancer Registry (NCR) database. Variables with demographic, treatment, and survival data were obtained. Survival curves were estimated by Kaplan–Meier's method, and the effect of prognostic factors on OS was assessed in a multivariable Cox regression analysis. Results A total of 4957 patients were identified. There were slightly more males (54.7%). Median age at diagnosis was 64 years, and 53.6% of the tumors were located in the extremities. Radiotherapy (RT) was administered to 2481 (50.1%) patients, and 252 (5.1%) patients were treated with perioperative systemic chemotherapy. The total use of perioperative RT did not significantly change in the last 20 years, but the timing followed clinical guidelines: preoperative RT increased significantly (2000–2008: 3.7%, 2009–2017: 22.3%; p < 0.001), whereas the use of postoperative RT diminished (2000–2008: 45.9%, 2009–2017: 26.1%; p < 0.001). The use of perioperative chemotherapy slightly decreased (2000–2008: 5.9%, 2009–2017: 4.4%; p = 0.015). 5-year OS was 59.6% (95% CI: 58.2–61.0). Sex, age, year of diagnosis, tumor location, tumor size, histological grade, depth, histological subtype, surgical margins, and the use of perioperative RT were identified as independent predictors for OS. Conclusion Preoperative RT is gradually replacing postoperative RT for localized STS in the Netherlands. The use of perioperative chemotherapy is rare and has slightly decreased in recent years. Identified baseline characteristics and treatment factors predicting OS may aid in future treatment decisions.

Circulating tumor DNA dynamics and recurrence risk in patients undergoing curative intent resection of colorectal cancer liver metastases: A prospective cohort study.

BackgroundIn patients with resectable colorectal liver metastases (CRLM), the role of pre- and postoperative systemic therapy continues to be debated. Previous studies have shown that circulating tumor DNA (ctDNA) analysis, as a marker of minimal residual disease, is a powerful prognostic factor in patients with nonmetastatic colorectal cancer (CRC). Serial analysis of ctDNA in patients with resectable CRLM could inform the optimal use of perioperative chemotherapy. Here, we performed a validation study to confirm the prognostic impact of postoperative ctDNA in resectable CRLM observed in a previous discovery study.Methods and findingsWe prospectively collected plasma samples from patients with resectable CRLM, including presurgical and postsurgical samples, serial samples during any pre- or postoperative chemotherapy, and serial samples in follow-up. Via targeted sequencing of 15 genes commonly mutated in CRC, we identified at least 1 somatic mutation in each patient’s tumor. We then designed a personalized assay to assess 1 mutation in plasma samples using the Safe-SeqS assay. A total of 380 plasma samples from 54 patients recruited from July 2011 to Dec 2014 were included in our analysis. Twenty-three (43%) patients received neoadjuvant chemotherapy, and 42 patients (78%) received adjuvant chemotherapy after surgery. Median follow-up was 51 months (interquartile range, 31 to 60 months). At least 1 somatic mutation was identified in all patients’ tumor tissue. ctDNA was detectable in 46/54 (85%) patients prior to any treatment and 12/49 (24%) patients after surgery. There was a median 40.93-fold (19.10 to 87.73, P < 0.001) decrease in ctDNA mutant allele fraction with neoadjuvant chemotherapy, but ctDNA clearance during neoadjuvant chemotherapy was not associated with a better recurrence-free survival (RFS). Patients with detectable postoperative ctDNA experienced a significantly lower RFS (HR 6.3; 95% CI 2.58 to 15.2; P < 0.001) and overall survival (HR 4.2; 95% CI 1.5 to 11.8; P < 0.001) compared to patients with undetectable ctDNA. For the 11 patients with detectable postoperative ctDNA who had serial ctDNA sampling during adjuvant chemotherapy, ctDNA clearance was observed in 3 patients, 2 of whom remained disease-free. All 8 patients with persistently detectable ctDNA after adjuvant chemotherapy have recurred. End-of-treatment (surgery +/− adjuvant chemotherapy) ctDNA detection was associated with a 5-year RFS of 0% compared to 75.6% for patients with an undetectable end-of-treatment ctDNA (HR 14.9; 95% CI 4.94 to 44.7; P < 0.001). Key limitations of the study include the small sample size and the potential for false-positive findings with multiple hypothesis testing.ConclusionsWe confirmed the prognostic impact of postsurgery and posttreatment ctDNA in patients with resected CRLM. The potential utility of serial ctDNA analysis during adjuvant chemotherapy as an early marker of treatment efficacy was also demonstrated. Further studies are required to define how to optimally integrate ctDNA analyses into decision-making regarding the use and timing of adjuvant therapy for resectable CRLM.Trial registrationACTRN12612000345886.