Direct surgery with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for patients with colorectal peritoneal metastases

IntroductionNeoadjuvant chemotherapy is widely used in treatment of peritoneal metastases from colorectal cancer, but there is little scientific evidence for this approach. This study aimed to study survival in patients treated with direct surgery with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), i.e. without neoadjuvant chemotherapy.Material and methodsPatients with histopathologically confirmed peritoneal metastases from colorectal cancer that underwent first-time CRS-HIPEC with complete cytoreduction (CC0 or 1) at Karolinska University Hospital 2012–2019 were included. Patients with synchronous extraperitoneal metastases were excluded if not treated before end of follow-up. Factors associated with overall survival (OS) and disease-free survival (DFS) were evaluated using the Kaplan-Meier method and Cox regression models. The multivariable models were adjusted for sex, age, synchronous/metachronous peritoneal metastases, peritoneal carcinomatosis index (PCI), extraperitoneal metastases and the pathological tumor (T) and lymph node (N) stage of the primary tumor.ResultsIn all, 131 patients underwent complete CRS-HIPEC for peritoneal metastases without neoadjuvant chemotherapy. The median OS and DFS were 40.3 months and 12.5 months, respectively, in patients treated with direct surgery. In the multivariable model, PCI≥16 was the only variable associated with decreased OS, whereas elevated PCI, metachronous development of peritoneal metastases and synchronous extraperitoneal metastases were associated with decreased DFS. Age was not associated with an impaired prognosis.ConclusionPatients who underwent direct surgery with CRS-HIPEC had a good prognosis, with a median OS of more than 3 years. The results from this study question the need of neoadjuvant chemotherapy in all patients eligible for CRS-HIPEC.     

The additive value of restaging-CT during neoadjuvant chemotherapy for gastric cancer

IntroductionComputed tomography (CT) is used for restaging of gastric cancer patients during neoadjuvant chemotherapy (NAC). The treatment strategy could be altered after detection of distant interval metastases, possibly leading to a reduction in unnecessary chemotherapy cycles, its related toxicity, and surgical procedures. The aim of this study was to evaluate the additive value of restaging-CT during NAC in guiding clinical decision making in gastric cancer.Materials and methodsThis retrospective, multicenter cohort study identified all patients with surgically resectable gastric adenocarcinoma (cT1–4a-x, N0–3-x, M0-x), who started NAC with curative intent. Restaging-CT was performed after 2 out of 3 cycles of NAC. The primary outcome was treatment alterations made based on restaging-CT by a multidisciplinary tumor board. Confirmation of metastases was obtained by surgery or biopsy.ResultsBetween 2007 and 2015, CT-restaging was performed in 122 out of 152 included patients and timed after 2 cycles (n = 76) or after 3 cycles (n = 46) of NAC. Restaging-CT revealed a metastasis in 1 out of 122 restaged patients (1%) after which surgical resection was omitted, whereas 4 patients (3%) with distant interval metastases were not identified by restaging-CT and underwent a futile laparotomy. In 5 out of 76 patients (7%) disease progression was detected while undergoing NAC, leading to omission of the 3rd cycle of chemotherapy.ConclusionThe additive value of restaging-CT during NAC in gastric cancer is limited in guiding clinical decision making and therefore not recommended. Further studies may identify subgroups that may benefit of alternative diagnostic modalities.     

Surrogate end-points for overall survival in 22 neoadjuvant trials of gastro-oesophageal cancers

BackgroundThe surrogacy between disease-free survival (DFS) and overall survival (OS) has been evaluated in patients with gastric cancer who received adjuvant chemotherapy. Similar analyses in patients who have undergone neoadjuvant chemoradiotherapy (CTRT) or chemotherapy (CT) for gastro-oesophageal (GE) cancer have not yet been performed.MethodsWe evaluated the correlation between DFS and pathologic complete response (pCR) with OS in patients with GE carcinomas enrolled in randomised studies. A weighted linear regression analysis was used to evaluate surrogacy. Correlations were evaluated by squared correlation R². Surrogacy of DFS and pCR with OS was assessed through the correlation between end-points and OS (individual-level surrogacy), and between the treatment effects on the end-points (trial-level surrogacy). Correlations were weighted by the number of patients in the intent-to-treat population.ResultsTwenty-two trials were included for a total of 4749 patients that received CTRT or CT for gastric or oesophageal cancers. Treatment effect on surrogates did not correlate with treatment effect on OS (R² = 0.27, and R² = 0.17, for DFS and pCR) at the trial level. In subgroup analysis surrogacy of DFS did not vary according to histology or treatment modality but was good in gastric cancer and poor in oesophageal cancers.ConclusionsDFS and pCR did not correlate with OS, and should not be used as surrogate end-points in patients with GE cancer who have undergone neoadjuvant therapy. OS should still represent the primary end-point to compare treatments in future randomised clinical trials.     

The yield of staging laparoscopy for resectable and borderline resectable pancreatic cancer in the PREOPANC randomized controlled trial

BackgroundThe necessity of the staging laparoscopy in patients with pancreatic cancer is still debated. The objective of this study was to assess the yield of staging laparoscopy for detecting occult metastases in patients with resectable or borderline resectable pancreatic cancer.MethodThis was a post-hoc analysis of the randomized controlled PREOPANC trial in which patients with resectable or borderline resectable pancreatic cancer were randomized between preoperative chemoradiotherapy or immediate surgery. Patients assigned to preoperative treatment underwent a staging laparoscopy prior to preoperative treatment according to protocol, to avoid unnecessary chemoradiotherapy in patients with occult metastatic disease.ResultsOf the 246 included patients, 7 did not undergo surgery. A staging laparoscopy was performed in 133 patients (55.6%) and explorative laparotomy in 106 patients (44.4%). At staging laparoscopy, occult metastases were detected in 13 patients (9.8%); 12 liver metastases and 1 peritoneal metastasis. At direct explorative laparotomy, occult metastases were found in 9 patients (8.5%); 6 with liver metastases, 1 with peritoneal metastases, and 2 with metastases at multiple sites. One patient had peritoneal metastases at exploration after a negative staging laparoscopy. Patients with occult metastases were more likely to receive palliative chemotherapy if found with staging laparoscopy compared to laparotomy (76.9% vs. 30.0%, p = 0.040).ConclusionsStaging laparoscopy detected occult metastases in about 10% of patients with resectable or borderline resectable pancreatic cancer. These patients were more likely to receive palliative systemic chemotherapy compared to patients in whom occult metastases were detected with laparotomy. A staging laparoscopy is recommended before planned resection.     

Volume-outcome relation in palliative systemic treatment of metastatic oesophagogastric cancer

IntroductionPalliative systemic therapy has been shown to improve survival in metastatic oesophagogastric cancer. Administration of palliative systemic therapy in metastatic oesophagogastric cancer varies between hospitals. We aimed to explore the association between the annual hospital volume of oesophagogastric cancer patients and survival.MethodsPatients diagnosed in the Netherlands between 2005 and 2013 with metastatic oesophagogastric cancer were identified in the Netherlands Cancer Registry. Patients were attributed according to three definitions of high volume: (1) high-volume incidence centre, (2) high-volume treatment centre and (3) high-volume surgical centre. Independent predictors for administration of palliative chemotherapy were evaluated by means of multivariable logistic regression analysis, and multivariable Cox proportional hazard regression analysis was performed to assess the impact of high-volume centres on survival.ResultsOur data set comprised 4078 patients with metastatic oesophageal cancer, and 5425 patients with metastatic gastric cancer, with a median overall survival of 20 weeks (95% confidence interval [CI] 19–21 weeks) and 16 weeks (95% CI 15–17 weeks), respectively. Patients with oesophageal cancer treated in a high-volume surgical centre (adjusted hazard ratio [HR] 0.80, 95% CI 0.70–0.91) and a high-volume treatment centre (adjusted HR 0.88, 95% CI 0.78–0.99) exhibited a decreased risk of death. For gastric cancer, patients treated in a high-volume surgical centre (adjusted HR 0.83, 95% CI 0.74–0.92) had a superior outcome.ConclusionImproved survival in patients undergoing palliative systemic therapy for oesophagogastric cancer was associated with treatment in high-volume treatment and surgical centres. Further research should be implemented to explore which specific factors of high-volume centres are associated with improved outcomes.     

The role of hepatectomy in the management of metastatic gastric adenocarcinoma: A systematic review

BackgroundGastric cancer has a high mortality, with many patients presenting with advanced disease. Many patients who undergo curative gastrectomy will subsequently develop metastatic disease. Hepatectomy has an established place in treating metastases from a variety of cancers but its role in gastric cancer is not clear. This review sought to systematically appraise the literature to establish the role of hepatectomy in treating gastric cancer metastases.MethodMedline and EMBASE were searched for all papers publishing data on survival of patients with metastatic gastric adenocarcinoma who underwent hepatectomy.ResultsSeventeen studies with 438 patients were included. There were no randomised controlled trials. Perioperative mortality was 2%, with morbidity between 17 and 60%. Patients with solitary metastases appeared to have better survival. Other favourable survival characteristics included unilobar disease, and metachronous presentation. No advantage was demonstrated with either adjuvant or neoadjuvant chemotherapy.DiscussionFew patients with hepatic metastases from gastric cancer are suitable for hepatectomy, but for those suitable there appears to be survival benefit. Patients with synchronous, multiple or bilobar metastases have worse survival.ConclusionThe evidence supporting the role of hepatectomy in the treatment of hepatic metastases from gastric cancer is weak. However in a selected group there appears to be a survival advantage; patients with solitary metastases had better survival outcomes than those with multiple metastases and metachronous presentation was associated with a better prognosis than synchronous presentation. Hepatectomy should be considered in these patients in the setting of a randomised trial.     

In real life,one-quarter of patients with hormone receptor-positive metastatic breast cancer receive chemotherapy as initial palliative therapy: a study of the Southeast Netherlands Breast Cancer Consortium

BackgroundThe objective of this study was to present initial systemic treatment choices and the outcome of hormone receptor-positive (HR+) metastatic breast cancer.Patients and methodsAll the 815 consecutive patients diagnosed with metastatic breast cancer in 2007–2009 in eight participating hospitals were identified. From the 611 patients with HR+ disease, a total of 520 patients with HER2-negative (HER2-) breast cancer were included. Initial palliative systemic treatment was registered. Progression-free survival (PFS) and overall survival (OS) per initial palliative systemic therapy were obtained using the Kaplan–Meier method and compared using the log-rank test.ResultsFrom the total of 520 patients with HR+/HER2- metastatic breast cancer, 482 patients (93%) received any palliative systemic therapy. Patients that received initial chemotherapy (n = 116) were significantly younger, had less comorbidity, had received more prior adjuvant systemic therapy and were less likely to have bone metastasis only compared with patients that received initial endocrine therapy (n = 366). Median PFS of initial palliative chemotherapy was 5.3 months [95% confidence interval (CI) 4.2–6.2] and of initial endocrine therapy 13.3 months (95% CI 11.3–15.5), with a median OS of 16.1 and 36.9 months, respectively. Initial chemotherapy was also associated with worse outcome in terms of PFS and OS after adjustment for prognostic factors.ConclusionsA high percentage of patients with HR+ disease received initial palliative chemotherapy, which was associated with worse outcome, even after adjustment of relevant prognostic factors.     

Upfront chemotherapy and short-course radiotherapy with delayed surgery for locally advanced rectal cancer with synchronous liver metastases

BackgroundThe optimal treatment of locally advanced rectal cancer with synchronous liver metastases remains controversial. In this study, we aimed to evaluate the safety, efficacy, and oncologic outcomes of upfront chemotherapy and short-course radiotherapy with delayed surgery in patients with locally advanced rectal cancer and synchronous liver metastases.MethodsForty-four patients who underwent upfront chemotherapy and short-course radiotherapy with delayed surgery for locally advanced rectal cancer (cT3/4, <2.0 mm from the mesorectal fascia) with synchronous liver metastases between January 2010 and June 2017 were reviewed retrospectively. Primary and metastatic liver lesions were resected with curative intent. Upfront chemotherapy and short-course radiotherapy were administered. Thereafter, restaging, surgery only, or additional chemotherapy followed by surgery was performed.ResultsAt the time of initial diagnosis, 20 patients had <3 liver metastases; 24 patients had ≥3 liver metastases. Twenty-three patients had hemi-liver metastases; 21 patients had bilobar liver metastases. R0 resection of rectal lesions was achieved in 43 patients. Synchronous R0 resection of liver metastases was achieved in 41 patients. Postoperative complications (Clavien–Dindo Grade ≥ III) were noted in 5 patients. Grade 3/4 adverse events were observed in 26 patients. All adverse events were managed effectively with medication and supportive care. The 3-year overall survival and progression-free survival rates were 65.3% and 26.9%, respectively.ConclusionUpfront chemotherapy and short-course radiotherapy with delayed surgery appear to be safe and effective in patients with locally advanced rectal cancer and synchronous liver metastases without substantially increasing treatment induced morbidity.     

Prognostic value of tumor regression grade following the administration of neoadjuvant chemotherapy as treatment for gastric/gastroesophageal adenocarcinoma: A meta-analysis of 14 published studies

IntroductionThe efficacy of neoadjuvant chemotherapy (NAC) for advanced gastric cancer (GC) has recently been revealed. The use of tumor regression grade (TRG) has also been reported, where TRG has been positively correlated with prognosis. However, previous studies included several types of GC and treatments. The prognostic value of TRG in a specific population has not been well investigated. Therefore, a meta-analysis of studies on gastric adenocarcinomas treated with NAC that evaluate the prognostic impact of TRG on overall survival (OS) must be conducted to provide more accurate evidence.MethodsA meta-analysis of studies reporting gastric cancer/gastroesophageal junction (GC/GEJ) adenocarcinoma treated with NAC was performed. Studies that calculate the number of responders and non-responders were considered eligible. The risk ratio (RR) was obtained from the eligible studies, and a random-effects model was used for pooled analysis.ResultsFourteen studies, which included a total of 1660 patients, were included in the current study. The responders showed better OS (RR: 0.53, 95% confidence interval (CI): 0.46–0.60, P < 0.001). All subgroup analyses (Asian vs. non-Asian populations, different TRGs, GC/GEJ vs. GC) also revealed the statistical dominance of better TRG over better OS. However, the possibility of some publication bias remained.ConclusionsIn this meta-analysis, better TRG was associated with better OS. However, the histology, configuration, and location of GC varied. Hence, a more subdivided analysis is recommended to obtain more solid evidence.     

Comparison of Neoadjuvant and Adjuvant Chemotherapy in Muscle-invasive Bladder Cancer

BackgroundWe use observational methods to compare impact of perioperative chemotherapy timing (ie, neoadjuvant and adjuvant) on overall survival (OS) in muscle-invasive bladder cancer because there is no head-to-head randomized trial, and patient factors may influence decision-making.Patients and MethodsUsing Surveillance, Epidemiology, and End Results-Medicare data, we identified patients receiving cystectomy for muscle-invasive bladder cancer diagnosed between 2004 and 2013. Patients were classified as receiving neoadjuvant or adjuvant chemotherapy. Propensity of receiving neoadjuvant chemotherapy was determined using gradient boosted models. Inverse probability of treatment weighted survival curves were adjusted for 13 demographic, socioeconomic, temporal, and oncologic covariates.ResultsWe identified 1342 patients who received neoadjuvant (n = 676) or adjuvant chemotherapy (n = 666) with a median follow-up of 23 months (interquartile range, 9-55 months). Inverse probability of treatment weighted adjustment allows comparison of the groups head-to-head as well as counterfactual scenarios (eg, effect if those getting one treatment were to receive the other). The average treatment effect (ie, “head-to-head” comparison) of adjuvant compared with neoadjuvant on OS was not significant (hazard ratio, 1.14; 95% confidence interval, 0.99-1.31). However, the average treatment effect of the treated (ie, the effect if the neoadjuvant patients were to receive adjuvant instead) was associated with a 33% increase in risk of mortality if they were given adjuvant therapy instead (hazard ratio, 1.33; 95% confidence interval, 1.12-1.57).ConclusionSignificant treatment selection bias was noted in peri-cystectomy timing, which limits the ability to discriminate differential efficacy of these 2 approaches with observational data. However, patients with higher propensity to receive neoadjuvant therapy were predicted to have increased OS with approach, in keeping with existing paradigms from trial data.     

Improved Overall Survival with Aggressive Primary Tumor Radiotherapy for Patients with Metastatic Esophageal Cancer

ObjectivesThe aim of this study was to characterize utilization and survival outcomes associated with primary tumor–directed radiotherapy (PTDRT) in patients with newly diagnosed metastatic esophageal cancer.MethodsWe conducted an observational cohort study using the National Cancer Data Base to evaluate patients with newly diagnosed metastatic esophageal cancer between 2004 and 2012. Overall survival outcomes after treatment with chemotherapy plus conventional palliative dose radiotherapy (<5040 cGy), chemotherapy plus definitive dose radiotherapy (≥5040 cGy), or chemotherapy alone were compared by using Cox proportional hazards models with inverse probability of treatment weighting using the propensity score. Potential unmeasured confounding was assessed through sensitivity analyses.ResultsThe final cohort consisted of 12,683 patients: 57% were treated with chemotherapy alone, 24% were treated with chemotherapy plus palliative dose radiotherapy, and 19% were treated with chemotherapy plus definitive dose radiotherapy. Compared with chemotherapy alone, chemotherapy plus definitive dose radiotherapy was associated with improved survival (median overall survival of 8.3 versus 11.3 months [hazard ratio = 0.72, 95% confidence interval: 0.70–0.74, p ≤ 0.001]), whereas chemotherapy plus palliative dose radiotherapy was associated with slightly inferior outcomes (median overall survival of 8.3 months versus 7.5 months (hazard ratio = 1.10, 95% confidence interval 1.07–1.13, p ≤ 0.001). These findings were robust to potential unmeasured confounding in sensitivity analyses. Additionally, landmark analyses confirmed these findings in patients surviving 12 months or longer.ConclusionsDefinitive dose, but not conventional palliative dose, PTDRT is associated with improved overall survival in metastatic esophageal cancer, suggesting that local control may be important to prognosis. These findings support integrating PTDRT into future clinical trials aimed at refining personalized treatment for patients with metastatic esophageal cancer.     

Improved Overall Survival With Comprehensive Local Consolidative Therapy in Synchronous Oligometastatic Non–Small-Cell Lung Cancer

BackgroundLocal consolidative therapy (LCT) to optimize disease control is an evolving management paradigm in non–small-cell lung cancer (NSCLC) patients who present with a limited metastatic disease burden. We hypothesized that LCT to all sites of disease would be associated with improved overall survival (OS) among patients with synchronous oligometastatic NSCLC.Patients and MethodsPatients presenting to a single institution (2000-2017) with stage IV NSCLC and ≤ 3 synchronous metastases were identified. Intrathoracic nodal disease was counted as one site. Landmark and propensity-adjusted Cox regression analyses were performed to identify factors associated with OS.ResultsOf 194 patients, 143 (74%) had 2 or 3 sites of metastasis. LCT was delivered to all sites of disease in 121 patients (62%), to some but not all sites in 52 (27%), and were not used in 21 (11%). Comprehensive LCT was independently associated with improved OS (hazard ratio [HR] = 0.67; 95% confidence interval [CI], 0.46-0.97; P = .034), with the greatest therapeutic effect among patients without thoracic nodal disease, bone metastases, or > 1 metastatic site. Among patients who underwent comprehensive LCT, tumor histology (squamous: HR = 2.32; 95% CI, 1.28-4.22; P = .006), intrathoracic disease burden (T3-4: HR = 1.67; 95% CI, 0.97-2.86; P = .065; N3: HR = 1.90; 95% CI, 0.90-4.03; P = .093), and bone metastases (HR = 1.74; 95% CI, 1.02-3.00; P = .044) were associated with poor OS.ConclusionComprehensive LCT was associated with improved OS in this large cohort of patients with synchronous oligometastatic NSCLC. These results support ongoing prospective efforts to characterize the therapeutic benefits associated with this management strategy.     

Early Start of Chemotherapy after Resection of Brain Metastasis from Colon Cancer with Synchronous Multiple Liver Metastases

Brain metastasis (BM) is infrequent in colorectal cancer (CRC) patients. Although BM from CRC is a late-stage phenomenon with an extremely poor prognosis, some subsets of patients would benefit from a multidisciplinary management strategy. The prognosis of patients with BM from CRC is associated with the curability of the therapy for BM and number of metastatic organs. The start of chemotherapy treatment usually requires a delay of about 4 weeks after surgical resection in patients with primary CRC having synchronous distant metastasis. However, there is no evidence to indicate the required length of this delay interval. In addition, there is a chance that a patient may die because postoperative chemotherapy was not started soon enough and a metastatic tumor was able to develop rapidly. Here, we present a case where combination chemotherapy with capecitabine and oxaliplatin (XELOX) was started within 1 week after resection of BM from colon cancer for synchronous multiple liver metastases. To our knowledge, this is the first report of the start of chemotherapy, involving treatments such as folinic acid, fluorouracil, and oxaliplatin (FOLFOX); folinic acid, fluorouracil, and irinotecan (FOLFIRI); and XELOX within 1 week after resection of BM from colon cancer with synchronous multiple liver metastases. These findings suggest possible changes in the start time of chemotherapy after surgery in the future.Key Words: Colorectal cancer, Chemotherapy, Brain metastasis, Surgery, XELOX     

Heterogeneity of first-line palliative systemic treatment in synchronous metastatic esophagogastric cancer patients: A real-world evidence study

The optimal first-line palliative systemic treatment strategy for metastatic esophagogastric cancer is not well defined. The aim of our study was to explore real-world use of first-line systemic treatment in esophagogastric cancer and assess the effect of treatment strategy on overall survival (OS), time to failure (TTF) of first-line treatment and toxicity. We selected synchronous metastatic esophagogastric cancer patients treated with systemic therapy (2010–2016) from the nationwide Netherlands Cancer Registry (n = 2,204). Systemic treatment strategies were divided into monotherapy, doublet and triplet chemotherapy, and trastuzumab-containing regimens. Data on OS were available for all patients, on TTF for patients diagnosed from 2010 to 2015 (n = 1,700), and on toxicity for patients diagnosed from 2010 to 2014 (n = 1,221). OS and TTF were analyzed using multivariable Cox regression, with adjustment for relevant tumor and patient characteristics. Up to 45 different systemic treatment regimens were found to be administered, with a median TTF of 4.6 and OS of 7.5 months. Most patients (45%) were treated with doublet chemotherapy; 34% received triplets, 10% monotherapy and 10% a trastuzumab-containing regimen. The highest median OS was found in patients receiving a trastuzumab-containing regimen (11.9 months). Triplet chemotherapy showed equal survival rates compared to doublets (OS: HR 0.92, 95%CI 0.83–1.02; TTF: HR 0.92, 95%CI 0.82–1.04) but significantly more grade 3–5 toxicity than doublets (33% vs. 21%, respectively). In conclusion, heterogeneity of first-line palliative systemic treatment in metastatic esophagogastric cancer patients is striking. Based on our data, doublet chemotherapy is the preferred treatment strategy because of similar survival and less toxicity compared to triplets.     

Synchronous peritoneal metastases of gastric cancer origin: incidence,treatment and survival of a nationwide Dutch cohort

Introduction

The peritoneum is a predilection site for gastric cancer metastases. Current standard treatment for gastric cancer patients with synchronous peritoneal metastases is palliative systemic therapy. However, its efficacy is largely unknown. The aim of this study was to investigate the incidence, treatment and survival patterns of gastric cancer patients with synchronous peritoneal metastases in the Netherlands.

Methods

All newly diagnosed gastric adenocarcinoma patients with synchronous peritoneal metastases between 1999 and 2017 were selected from the Netherlands Cancer Registry (NCR). Incidence, treatment and survival patterns were analyzed.

Results

In total, 3,773 patients were identified from the NCR. The incidence of synchronous peritoneal metastases in gastric cancer patients increased from 18% in 2008 to 27% in 2017. The use of systemic therapy increased from 15% in 1999–2002 to 43% in 2013–2017 (p?<?0.001). The median survival of the entire cohort did not significantly increase over time. Median survival of patients treated with systemic therapy increased from 7.4 months in 1999–2002 to 9.4 months in 2013–2017 (p?=?0.005). In contrast, median survival of patients not treated with systemic therapy decreased from 3.3 months in 1999–2002 to 2.1 months in 2013–2017 (p?<?0.001). Some clinical and pathological data such as the extent of the peritoneal metastases were not available.

Conclusion

Synchronous peritoneal metastases are increasingly diagnosed in gastric cancer patients. In recent years, more patients were treated with systemic treatment and survival of these patients increased. However, as survival of the entire group did not improve over time, the effect of systemic therapy remains unknown.

     

Early start of chemotherapy after resection of primary colon cancer with synchronous multiple liver metastases: a case report

The start of chemotherapy treatment usually requires a delay of about 4 weeks after surgical resection in patients with primary colorectal cancer and synchronous distant metastasis. However, there is no evidence to indicate the required length of this delay interval. In addition, there is a chance that a patient may die because postoperative chemotherapy was not started soon enough and a metastatic tumor was able to develop rapidly. Here, we present a case in which combination chemotherapy with capecitabine and oxaliplatin (XELOX) was started within 1 week after a right hemicolectomy for synchronous multiple liver metastases. To our knowledge, this is the first report of the start of chemotherapy, involving treatments such as folinic acid, fluorouracil, and oxaliplatin (FOLFOX); folinic acid, fluorouracil, and irinotecan (FOLFIRI); and XELOX, within 1 week after a colorectal cancer operation with anastomosis. The findings suggest possible changes in the start time of chemotherapy after surgery in the future.     

Peritoneal metastases in elderly patients with colorectal cancer

BackgroundWith the introduction of cytoreductive surgery with intraperitoneal chemotherapy and the development of new systemic anti-cancer agents, the treatment of colorectal cancer (CRC) patients with peritoneal metastases has changed. Real-world data on the treatment of elderly patients and their clinical outcomes is lacking.MethodsAll CRC patients diagnosed with synchronous peritoneal metastases (SPM) during 2008–2019 (n = 7,748) were identified from the Netherlands Cancer Registry. Trends in treatment and postoperative mortality were described by age category (<70, 70–74, 75–79, ≥80 years) and period of diagnosis (2008–2013, 2014–2019). Kaplan-Meier curves were constructed, and log-rank tests were performed to evaluate differences in overall survival (OS).ResultsWith increasing age, less patients received multimodality treatment and systemic treatment. Of the patients aged <70 years, 38% underwent multimodality treatment and 35% palliative systemic therapy, declining to 4% and 12% in patients ≥80 years. A large and increasing proportion of elderly patients did not receive cancer-directed treatment, this increased from 32% in 2008–2013 to 41% in 2014–2019 in 75–79 years old patients and from 52% to 65% in ≥80 years old. Postoperative mortality decreased in all age categories over time, OS remained stable. The median OS of elderly patients ranged from 8 months in 70–74 years old to 3 months in patients aged ≥80 years.DiscussionAge strongly affects treatment of patients with SPM, with a large and increasing proportion of elderly patients not receiving cancer-directed treatment. Their prognosis remains very poor. There is a need for therapeutic options that are well tolerable for elderly patients.     

An observational retrospective analysis of the main metastatic site and corresponding locoregional treatment as a prognostic factor in metastatic gastric cancer

Despite novel drugs, the prognosis for patients with metastatic gastric cancer remains poor. In rare instances, locoregional therapies are used in addition to standard chemotherapy in patients with oligometastatic involvement. This type of approach has not been supported by solid published evidence. The aim of the present retrospective study was to assess the prognostic impact of factors such as metastatic site, tumour histology and locoregional treatment in patients with metastatic gastric cancer. A total of 184 patients with metastatic gastric or gastroesophageal junction adenocarcinoma who received at least one line of palliative therapy with doublet or triplet chemotherapy were enrolled in the current analysis. Median overall survival (OS) was 8.32 months (95% CI, 7.02–9.41) and median progression-free survival (PFS) was 4.16 months (95% CI, 3.24–5.08). Lung metastases vs. other sites of metastatic involvement [hazard ratio (HR), 0.27; P=0.0133] and intestinal histology (HR, 0.48; P=0.08) were significantly associated with an improved OS. Improved PFS was also observed (HR, 0.49; P=0.10 and HR, 0.72; P=0.08 for lung metastases and intestinal histology, respectively). Second line chemotherapy and locoregional treatment of metastases (surgery or radiotherapy) were associated with improved OS (HR, 0.52; P<0.0001 and HR, 0.35; P<0.0001, respectively). Multivariate analysis confirmed an independent prognostic role for OS only for locoregional treatment, second line treatment and intestinal histology. The present results suggested that the presence of lung metastases alone was not a relevant prognostic factor and was influenced by the availability of further lines of treatment or by locoregional treatments. Locoregional treatments in patients with oligometastatic disease should be offered as they allow prolonged survival in patients with otherwise relatively short life expectancy.     

The addition of chemoradiation to adjuvant chemotherapy is associated with improved survival in lymph node-positive gastric cancer

BackgroundIn the ARTIST trial, chemoradiation did not improve disease-free survival (DFS) in gastric cancer patients treated with curative-intent surgery and adjuvant chemotherapy. Subgroup analysis suggested chemoradiation improved DFS in patients with lymph node (LN) metastases, but the role of adjuvant chemoradiation remains uncertain. This study sought to determine the role of adjuvant chemoradiation using population-based methods.MethodsSurveillance, Epidemiology and End Results-Medicare linked data from 2004 to 2013 was used to identify patients aged 66 and older with LN-positive gastric adenocarcinoma. Multivariable logistic regression evaluated factors associated with receipt of chemoradiation. The Kaplan-Meier method and Cox proportional hazards modeling were used to evaluate overall survival (OS).ResultsA total of 2409 patients with LN-positive gastric adenocarcinoma who underwent upfront surgical resection were identified; 309 (13%) received adjuvant chemotherapy and 407 (17%) received adjuvant chemotherapy and chemoradiation. Among all patients, median OS was 15 months. Median OS was 20 months for patients who received chemotherapy alone and 27 months for patients who received chemotherapy and chemoradiation (p < 0.05). Recent diagnosis, older age, tumor stage T3 or T4, and Charleston Comorbidity Index were associated with an increased hazard ratio for death (p < 0.05). Receipt of chemoradiation was associated with a decreased hazard ratio for death (p < 0.05).ConclusionsIn patients with LN-positive gastric adenocarcinoma, the addition of chemoradiation to adjuvant chemotherapy after upfront surgical resection was associated with improved survival irrespective of the extent of lymphadenectomy. These data suggest chemoradiation should be considered in patients with LN-positive gastric adenocarcinoma.     

Prognosis of metastatic gastric and gastroesophageal junction cancer by HER2 status: a European and USA International collaborative analysis

BackgroundTo determine whether human epidermal growth factor receptor 2 (HER2) status is an independent prognostic factor in metastatic gastric and gastroesophageal junction (GEJ) adenocarcinoma.Patients and methodsFormalin-fixed paraffin-embedded tumor samples from 381 metastatic gastric/GEJ cancer patients enrolled at Krankenhaus Nordwest and Memorial Sloan–Kettering Cancer Centers on six first-line trials of chemotherapy without trastuzumab were examined for HER2 by immunohistochemistry (IHC) and in situ hybridization (ISH). IHC 3+ or ISH-positive tumors were considered HER2 positive.ResultsSeventy-eight of 381 patients (20%) had HER2-positive disease. In the multivariate logistic model, there were significantly higher rates of HER2 positivity in patients with liver metastasis (liver metastasis 31%; no liver metastasis 11%; P = 0.025) and intestinal histology (intestinal 33%; diffuse/mixed 8%; P = 0.001). No significant differences in HER2 positivity were found between resections and biopsies or primaries and metastases. Patients with HER2-positive gastric cancer had longer median overall survival compared with HER2-negative gastric cancer patients (13.9 versus 11.4 months, P = 0.047), but multivariate analysis indicated that HER2 status was not an independent prognostic factor (hazard ratio 0.79; 0.44–1.14; P = 0.194).ConclusionsApproximately 20% of Western patients with metastatic gastric cancer are HER2 positive. Unlike breast cancer, HER2 positivity is not independently prognostic of patient outcome in metastatic gastric or GEJ.