Gastric cancer with peritoneal metastases: a single center outline and comparison of different surgical and intraperitoneal treatments.

INTRODUCTION: Gastric cancer with peritoneal metastasis (GCPM) has an unfavourable prognosis. Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC) are promising treatment options that have been shown to improve survival. The aim of this study was to assess the impact of different treatments such as systemic chemotherapy, systemic chemotherapy + PIPAC, and CRS + HIPEC in patients with GCPM. MATERIAL AND METHODS: This single-centre retrospective study included 82 patients with GCPM treated between January 2016 and June 2021. After first-line chemotherapy, depending on disease response and burden, the patients were divided into three treatment groups: chemotherapy alone, chemotherapy + PIPAC, and CRS + HIPEC. The primary outcome was overall survival (OS) from diagnosis, which was compared among the treatment groups. RESULTS: Thirty-seven (45.1%) patients were administered systemic chemotherapy alone, 25 (30.4%) received chemotherapy + PIPAC, and 20 (24.4%) underwent CRS + HIPEC. The CRS + HIPEC group had better OS (median 24 months) than the PIPAC group (15 months, p = 0.01) and chemotherapy group (5 months, p = 0.0001). Following CRS + HIPEC, the postoperative grade 3-4 complication rate was 25%, and no postoperative in-hospital deaths occurred. The median disease-free survival (DFS) was 12 months. Multivariate analysis identified peritoneal carcinomatosis index (PCI) > 7 as an independent predictor of worse DFS. No independent predictors of OS were identified. CONCLUSION: Among patients with GCPM, we identified a highly selected population with oligometastatic disease. In this group, CRS + HIPEC provided a significant survival advantage with an acceptable major complication rate compared with other available therapies (systemic chemotherapy alone or in combination with PIPAC).

Predictive value of NLR, TILs (CD4+/CD8+) and PD-L1 expression for prognosis and response to preoperative chemotherapy in gastric cancer.

The combination of perioperative chemotherapy plus complete surgical resection is currently accounted as the first-choice strategy in patients with locally advanced Gastric Cancer (LAGC). Nevertheless, the partial response rate makes it necessary to search biological parameters useful to select patients who would benefit most from neoadjuvant chemotherapy (NAD-CT). We performed a retrospective analysis on a cohort of 65 LAGC cases, EBV negative and without MMR defect, submitted to perioperative chemotherapy plus surgical resection. We evaluated the neutrophil-lymphocytes ratio (NLR) in peripheral blood, the TILs density (reported as CD4/CD8 tissue ratio) and PD-L1 expression by immunohistochemistry on bioptic tissues before the treatment. Results were correlated with the biological features, histological response (TRG) and clinical outcome (PFS and OS). We found that NLR, TILs and PD-L1 expression showed a significant correlation with TNM stage, lymphovascular invasion and response to NAD-CT (TRG). Correlating the NLR, TILs and PD-L1 expression with PFS and OS, we found that patients with lower NLR levels (< 2.5 ratio), lower TILs (< 0.2 ratio) and higher PD-L1 level (CPS ≥ 1) had a significantly better PFS and OS than those with higher NLR, higher TILs and lower PD-L1 expression (p < 0.0001). Multivariate and multiple regression analyses confirmed the predictive and prognostic role of all three parameters, especially when all three parameters are combined. Our study demonstrated that pre-treatment NLR, TILs and PD-L1 expression are predictive and prognostic parameters in NAD-CT-treated LAGC suggesting a pivotal role of the systemic and tumor microenvironment immunological profile in the response to chemotherapy.

Results of the observational prospective RealFLOT study.

BACKGROUND: Perioperative FLOT (5-fluorouracil, oxaliplatin and docetaxel) has recently become the gold standard treatment for fit patients with operable gastric (GC) or gastroesophageal (GEJ) adenocarcinoma, getting a 5-year overall survival (OS) of 45%, over 23% with surgery alone. METHODS: RealFLOT is an Italian, multicentric, observational trial, collecting data from patients with resectable GC or GEJ adenocarcinoma treated with perioperative FLOT. Aim of the study was to describe feasibility and safety of FLOT, pathological complete response rate (pCR), surgical outcomes and overall response rate (ORR) in an unselected real-world population. Additional analyses evaluated the correlation between pCR and survival and the prognostic role of microsatellite instability (MSI) status. RESULTS: Of 206 patients enrolled that received perioperative FLOT at 15 Italian centers, 124 (60.2%) received at least 4 full-dose cycles, 190 (92.2%) underwent surgery, and 142 (68.9%) started the postoperative phase. Among patients who started the postoperative phase, 105 (51.0%) received FLOT, while 37 (18%) received de-intensified regimens, depending on clinical condition or previous toxicities. pCR was achieved in 7.3% of cases. Safety profile was consistent with literature. Neutropenia was the most common G 3-4 adverse event (AE): 19.9% in the preoperative phase and 16.9% in the postoperative phase. No toxic death was observed and 30-day postoperative mortality rate was 1.0%. ORR was 45.6% and disease control rate (DCR) was 94.2%. Disease-free survival (DFS) and OS were significantly longer in case of pCR (p = 0.009 and p = 0.023, respectively). A trend towards better DFS was observed among MSI-H patients. CONCLUSIONS: These real-world data confirm the feasibility of FLOT in an unselected population, representative of the clinical practice. pCR rate was lower than expected, nevertheless we confirm pCR as a predictive parameter of survival. In addition, MSI-H status seems to be a positive prognostic marker also in patients treated with taxane-containing triplets.

Appropriateness of trifluridine/tipiracil in the clinical practice of third-line therapy in metastatic colorectal cancer.

Aim: To help to remove misperception of an appropriate position of trifluridine/tipiracil (FTD/TPI) in the treatment of metastatic colorectal cancer. Materials & methods: The RAND Corporation/UCLA Appropriateness Method was used by a panel of Italian experts to develop recommendations concerning daily practice with FTD/TPI. Forty-three clinical scenarios were discussed in two rounds and the resulting statements were rated as appropriate, uncertain or inappropriate, according to the median score. Results: Several topics were dealt with, covering the profile of eligible patients, therapeutic options beyond the second line, the practice of treatment with FTD/TPI, evaluation and efficacy and toxicity, as well as costs and compliance. Conclusion: FTD/TPI is an important therapeutic resource in refractory metastatic colorectal cancer that combines manageability and safety.

Lay abstract To remove misperception of trifluridine/tipiracil (FTD/TPI) in the treatment of metastatic colorectal cancer. An established Method for evaluating appropriateness of new drugs was used. Forty-three clinical scenarios were discussed in two rounds and the resulting statements were rated as appropriate, uncertain or inappropriate, according to the median score. Several topics were dealt with, covering the profile of eligible patients, therapeutic options beyond the second line, efficacy and toxicity, as well as compliance. FTD/TPI is an important therapeutic resource in refractory metastatic colorectal cancer that combines manageability and safety.

A detailed analysis of the recurrence timing and pattern after curative surgery in patients undergoing neoadjuvant therapy or upfront surgery for gastric cancer.

BACKGROUND AND OBJECTIVES: The aim of this study was to determine whether the administration of neoadjuvant therapy (NAD) affects the incidence, timing, and pattern of recurrence in patients treated by curative gastrectomy. METHODS: Sixty-nine patients undergoing NAD and R0 gastrectomy were compared with 198 patients undergoing upfront surgery using the propensity score matching (PSM) method. Disease-free survival (DFS), disease-specific survival (DSS), and progression-free survival (PFS) analyses were conducted with a log-rank test and Cox regression. Risk factors for recurrence were assessed by logistic regression. RESULTS: Among 69 patients with NAD, 28 (40.6%) experienced recurrence, and signet-ring cell (SRC) carcinoma was the only factor independently associated with recurrence. In the whole sample, NAD did not influence DFS, DSS, rate of recurrence, or PFS. After PSM, the variables associated with DFS were cN1, type of gastrectomy, the presence of SRCs, and the presence of lymphovascular invasion. Variables independently associated with recurrence were cN1, type of gastrectomy, and the presence of SRCs. CONCLUSIONS: NAD had no impact on DFS, DSS, or the pattern of recurrence in any patients with gastric cancer. To define a better treatment strategy, future studies should focus on subtypes that do not respond to the current neoadjuvant regimens.

DEBIRI plus capecitabine: a treatment option for refractory liver-dominant metastases from colorectal cancer.

Aim: This single institution Phase II study evaluated drug-eluting beads loaded with irinotecan (DEBIRI) plus capecitabine in pretreated patients with colorectal cancer liver metastases. Patients & methods: Forty patients with liver-limited or liver-dominant disease, who have failed at least two previous lines of chemotherapy, underwent either four DEBIRI at 2-week interval or two DEBIRI every 4 weeks for bilobar or single-lobe metastases, respectively. Capecitabine was given at 1000 mg/m2 twice-daily on days 1-14 every 3 weeks. Results: Seven partial responses and 12 stable diseases were observed, achieving a disease control rate of 47.5%. Median progression-free survival and overall survival resulted 4 and 8 months, respectively. Grade 3 adverse events occurred in 6/40 points (15%) of patients. Conclusion: DEBIRI plus capecitabine is a valid treatment option for heavily pretreated patients with colorectal cancer liver metastases.

Malignant Pleural Mesothelioma: Is Tailoring the Second-Line Therapy Really "Raising the Bar?"

OPINION STATEMENT: Unresectable or relapsed malignant pleural mesothelioma (MPM) has dismal prognosis. First-line combination therapy with pemetrexed and a platinum analog allows a modest survival benefit, while no clear therapeutic options exist for the second-line therapy. In this setting, pemetrexed seems to be the most active drug; however, the inclusion in front-line treatment limits its use in further lines. Nevertheless, rechallenge with one or both drugs used in first-line remains a feasible strategy for responder patients. Alternatively, only few cytotoxic drugs have demonstrated a mild activity in refractory MPM. Among other options, targeted therapy has unfortunately produced disappointing results as salvage treatment probably due to the lack of a clear understanding of the tumor biology. In contrast, recent data suggest moderate efficacy and mild toxicity of immunotherapy also for the treatment of MPM. The combination of checkpoint inhibitors with chemotherapy or other immunological agents seems promising and could really "raise the bar" in this setting.

Does sarcopenia affect outcome in patients with non-small-cell lung cancer harboring EGFR mutations?

AIM: To evaluate gefitinib outcomes in EGFR-mutated non-small-cell lung cancer (NSCLC) patients harboring EGFR mutations, according to their sarcopenia status. PATIENTS & METHODS: We retrospectively evaluated 33 patients with advanced NSCLC and EGFR mutations (exon 19 or 21), dividing them into sarcopenic patients, with low skeletal muscle index ≤39 cm2/m2 for women and ≤55 cm2/m2 for men, and nonsarcopenic patients. RESULTS: Sarcopenia does not affect response to gefitinib treatment in EGFR mutated NSCLC patients, even if it is a bad prognostic indicator for overall survival (p = 0.035). CONCLUSION: Early recognition of sarcopenia is beneficial for prevention of cancer cachexia and detection of patients at potential risk of serious adverse events. Gefitinib dosage should be reduced and modulated in sarcopenic patients.

Maintenance hormonal and chemotherapy treatment in metastatic breast cancer: a systematic review.

Endocrine treatment is the first-line therapy in hormone-sensitive metastatic breast cancer while chemotherapy is the first option in tumors refractory to endocrine therapy and in hormone-negative disease. Optimal duration, efficacy and safety of a maintenance endocrine therapy or chemotherapy after an induction treatment are still a matter of debate. We performed a literature review to identify studies regarding maintenance hormonal and chemotherapy treatments in metastatic breast cancer. We analyzed data relating to efficacy (improvement of progression-free survival and overall survival) and safety (symptoms relief and quality of life [QoL]). Maintenance endocrine therapy could prolong progression-free survival with a better control of symptoms and improving QoL. Maintenance chemotherapy prolong the response to a previous treatment, worsening the QoL, except for metronomic capecitabine.

From 2000 to 2016: Which Second-Line Treatment in Advanced Non-Small Cell Lung Cancer?

OPINION STATEMENT: New treatments-as immunotherapies and new antiangiogenic agents-are now available in second-line setting for patients affected by EGFR wild-type and ALK-negative non-small-cell lung cancer (NSCLC). Nintedanib, ramucirumab, nivolumab and pembrolizumab have to be included in the therapeutic sequences for patients affected by NSCLC, but no clear selection criteria are to date offered, except for patients with PD-L1 expression ≥50 %. Performance status, smoking habits and comorbidities should be considered as clinical criteria in order to select the appropriate treatment, but also tumour characteristics as histotype, platinum resistance and rapid progression after a first-line therapy should be taken into account. The aim of the present paper is to identify subgroups of patients eligible for different therapy sequences.

Gastric Cancer, Immunotherapy, and Nutrition: The Role of Microbiota.

Immune checkpoint inhibitors (ICI) have revolutionized the treatment of gastric cancer (GC), which still represents the third leading cause of cancer-related death in Western countries. However, ICI treatment outcomes vary between individuals and need to be optimized. Recent studies have shown that gut microbiota could represent a key influencer of immunotherapy responses. At the same time, the nutritional status and diet of GC patients are also predictive of immunotherapy treatment response and survival outcomes. The objective of this narrative review is to gather recent findings about the complex relationships between the oral, gastric, and gut bacterial communities, dietary factors/nutritional parameters, and immunotherapy responses. Perigastric/gut microbiota compositions/functions and their metabolites could be predictive of response to immunotherapy in GC patients and even overall survival. At the same time, the strong influence of diet on the composition of the microbiota could have consequences on immunotherapy responses through the impact of muscle mass in GC patients during immunotherapy. Future studies are needed to define more precisely the dietary factors, such as adequate daily intake of prebiotics, that could counteract the dysbiosis of the GC microbiota and the impaired nutritional status, improving the clinical outcomes of GC patients during immunotherapy.

Benefit of a multimodal approach combining chemotherapy and surgery in oligometastatic gastric cancer: experience from a tertiary referral center.

Introduction: Gastric cancer (GC) is the fourth leading cause of cancer-related death worldwide with limited therapeutic options. The aim of this study was to analyze the value of adding surgery to the first-line treatment in patients with oligometastatic GC (OGC). Methods: This retrospective study included patients with OGC who underwent induction chemotherapy followed by surgery of both primary tumor and synchronous metastasis between April 2012 and April 2022. Endpoints were overall survival (OS) and relapse-free survival (RFS) analyzed by the Kaplan-Meier method. Prognostic factors were assessed with the Cox model. Results: Data from 39 patients were collected. All cases were referred to our multidisciplinary tumor board (MTB) to evaluate the feasibility of radical surgery. After a median follow-up of 33.6 months (mo.), median OS was 26.6 mo. (95% CI 23.8-29.4) and median RFS was 10.6 mo. (95% CI 6.3-14.8). Pathologic response according to the Mandard criteria (TRG 1-3, not reached versus 20.5 mo. for TRG 4-5; HR 0.23, p=0.019), PS ECOG ≤ 1 (26.7 mo. for PS ≤ 1 versus 11.2 mo. for PS >1; HR 0.3, p=0.022) and a low metastatic burden (26.7 mo. for single site versus 12.9 mo. for ≥2 sites; HR 0.34, p=0.039) were related to good prognosis. No major intraoperative complications nor surgery-related deaths occurred in our series. Discussion: A sequential strategy of preoperative chemotherapy and radical surgical excision of both primary tumor and metastases was demonstrated to significantly improve OS and RFS. Multidisciplinary evaluation is mandatory to identify patients who could benefit from this strategy.

The Role of Staging Laparoscopy for Gastric Cancer Patients: Current Evidence and Future Perspectives.

A significant proportion of patients diagnosed with gastric cancer is discovered with peritoneal metastases at laparotomy. Despite the continuous improvement in the performance of radiological imaging, the preoperative recognition of such an advanced disease is still challenging during the diagnostic work-up, since the sensitivity of CT scans to peritoneal carcinomatosis is not always adequate. Staging laparoscopy offers the chance to significantly increase the rate of promptly diagnosed peritoneal metastases, thus reducing the number of unnecessary laparotomies and modifying the initial treatment strategy of gastric cancer. The aim of this review was to provide a comprehensive summary of the current literature regarding the role of staging laparoscopy in the management of gastric cancer. Indications, techniques, accuracy, advantages, and limitations of staging laparoscopy and peritoneal cytology were discussed. Furthermore, a focus on current evidence regarding the application of artificial intelligence and image-guided surgery in staging laparoscopy was included in order to provide a picture of the future perspectives of this technique and its integration with modern tools in the preoperative management of gastric cancer.

Surgery for locally advanced gastric cancer in the era of neoadjuvant therapies: something new?

BACKGROUND: Locally advanced gastric cancer (LAGC) represents a therapeutic challenge, particularly as it often involves adjacent organs. The necessity of neoadjuvant treatments for LAGC patients is still controversial. The aim of this study was to analyze the factors affecting prognosis and survival in patients with LAGC with particular regard to the effect of neoadjuvant therapies. METHODS: Between January 2005 and December 2018, the medical records of 113 patients with LAGC who underwent curative resection were retrospectively reviewed. Patient characteristics, related complications, long-term survival, and prognostic factors were analyzed at uni- and multivariate analyses. RESULTS: Postoperative mortality and morbidity rates of patients undergoing neo-adjuvant therapies were 2.3% and 43.2%, respectively. Whereas in patients undergoing upfront surgery were 4.6% and 26.1%, respectively. R0 resection was achieved 79.5% and in 73.9% of patients undergoing neoadjuvant therapy and upfront surgery, respectively (P<0.001). Multivariate analysis revealed that neoadjuvant therapy, completeness of resection (R0), number of lymph nodes retrieved, N status and the adoption of hyperthermic intraperitoneal chemotherapy were independent prognostic factors associated with longer survival. Five-year overall survival for NAC group and upfront surgery group was 46% and 32%, respectively (P=0.04). Five-year disease-free survival for NAC group and upfront surgery group was 38% and 25%, respectively (P=0.02). CONCLUSIONS: Patients with LAGC undergoing surgery plus neoadjuvant therapy had a better OS and DFS with respect to patients treated with surgery alone.

Pattern of recurrence and overall survival in esophagogastric cancer after perioperative FLOT and clinical outcomes in MSI-H population: the PROSECCO Study.

BACKGROUND: FLOT regimen is the standard perioperative treatment in Western countries for patients with locally advanced gastric (GC) or gastroesophageal junction cancer (GEJC). High microsatellite instability (MSI-H) and Mismatch Repair deficient (dMMR) demonstrated a favorable prognostic role and a concomitant negative predictive impact on the benefit of perioperative 5-fluorouracil-based doublets; however, its role in pts receiving FLOT chemotherapy is still unclear. METHODS: This is a retrospective, multicenter observational study of 265 pts with GC/GEJC treated with perioperative FLOT regimen in 11 Italian oncology centers between January 2017 to December 2021 and analyzed for microsatellite status. RESULTS: The MSI-H phenotype was found in 27 (10.2%) of 265 analyzed tumors. Compared to microsatellite stable (MSS) and Mismatch Repair proficient (pMMR) cases, MSI-H/dMMR were more frequently female (48.1% vs. 27.3%, p = 0.0424), elderly pts (age > 70 years, 44.4% vs. 13.4%, p = 0.0003), Laurens's intestinal type (62.5% vs. 36.1%, p = 0.02) and pts with a primary location tumor in the antrum (37 vs. 14.3%, p = 0.0004). A statistically significant difference in the rate of pathologically negative lymph node emerged (63% vs 30.7%, p = 0.0018). Compared to the MSS/pMMR tumor population, the MSI-H/dMMR subgroup had a better DFS (median not reached [NR] vs. 19.5 [15.59-23.59] mos, p = 0.031) and OS (median NR vs. 34.84 [26.68-47.60] mos, p = 0.0316). CONCLUSIONS: These real-world data confirm that FLOT treatment is effective in daily clinical practice for locally advanced GC/GEJC, also in the MSI-H/dMMR subgroup. It also showed a higher rate of nodal status downstaging and a better outcome of MSI-H/dMMR pts in comparison to MSS/pMMR.

The Impact of NUTRItional Status at First Medical Oncology Visit on Clinical Outcomes: The NUTRIONCO Study.

Malnutrition affects up to 75% of cancer patients and results from a combination of anorexia and metabolic dysregulation. Metabolic and nutritional abnormalities in cancer patients can lead to cachexia, a multifactorial syndrome characterized by involuntary loss of skeletal muscle mass, systemic inflammation and increased protein catabolism. Cancer cachexia negatively affects patients' outcomes, response to anticancer treatments, quality of life, and survival. However, risk of malnutrition, and cachexia are still under-recognized in cancer patients. The Prevalence of Malnutrition in Oncology (PreMiO) study revealed that 51% of patients already had nutritional deficiencies at their first medical oncology visit. Here, we report the results of the subsequent retrospective, observational NUTRItional status at first medical oncology visit ON Clinical Outcomes (NUTRIONCO) study, aimed at assessing the impact of baseline nutritional and non-nutritional variables collected in the PreMiO study on the clinical outcomes of the same patients followed up from August 2019 to October 2021. We have highlighted a statistically significant association between baseline variables and patient death, rehospitalization, treatment toxicity, and disease progression at follow-up. We found a higher overall survival probability in the well-nourished general study population vs. malnourished patients (p < 0.001). Of major interest is the fact that patient stratification revealed that malnutrition decreased survival probability in non-metastatic patients but not in metastatic patients (p < 0.001). Multivariate analysis confirmed that baseline malnutrition (p = 0.004) and VAS score for appetite loss (p = 0.0104), in addition to albumin < 35 g/L (p < 0.0001) and neutrophil/lymphocyte ratio > 3 (p = 0.0007), were independently associated with the death of non-metastatic patients at follow-up. These findings highlight the importance of proactive, early management of malnutrition and cachexia in cancer patients, and in particular, in non-metastatic patients, from the perspective of a substantial improvement of their clinical outcomes.

Enhanced recovery after surgery (ERAS) versus standard recovery for gastric cancer patients: The evidences and the issues.

The significant advances that have been reached, in the last decades, in the treatment of gastric cancer, contributed to the concept of enhanced recovery after surgery (ERAS) with the aim to reduce the surgical stress, accelerate postoperative recovery, and reduce the length of hospital stay. The most important items included in the ERAS protocols are the pre-operative patient education, early mobilization and immediate oral intake from the first postoperative day. The aim of this narrative review is to focus the attention on the possible advantages of ERAS program on perioperative functional recovery outcomes after gastrectomy for gastric cancer.

The Role of Surgery in the Management of Gastric Cancer: State of the Art.

Surgery still represents the mainstay of treatment of all stages of gastric cancer (GC). Surgical resections represent potentially curative options in the case of early GC with a low risk of node metastasis. Sentinel lymph node biopsy and indocyanine green fluorescence are novel techniques which may improve the employment of stomach-sparing procedures, ameliorating quality of life without compromising oncological radicality. Nonetheless, the diffusion of these techniques is limited in Western countries. Conversely, radical gastrectomy with extensive lymphadenectomy and multimodal treatment represents a valid option in the case of advanced GC. Differences between Eastern and Western recommendations still exist, and the optimal multimodal strategy is still a matter of investigation. Recent chemotherapy protocols have made surgery available for patients with oligometastatic disease. In this context, intraperitoneal administration of chemotherapy via HIPEC or PIPAC has emerged as an alternative weapon for patients with peritoneal carcinomatosis. In conclusion, the surgical management of GC is still evolving together with the multimodal strategy. It is mandatory for surgeons to be conscious of the current evolution of the surgical management of GC in the era of multidisciplinary and tailored medicine.

Safety and Efficacy of a First-Line Chemotherapy Tailored by G8 Score in Elderly Metastatic or Locally Advanced Gastric and Gastro-Esophageal Cancer Patients: A Real-World Analysis.

Introduction: Gastric (GC) and gastro-esophageal cancer (GEC) are common neoplasms in the elderly. However, in clinical practice, the correct strategy for elderly patients who might benefit from chemotherapy (CT) is unknown. Prospective data are still poor. In this context, we performed a retrospective analysis of GC patients aged ≥75 years and treated at our institutions. Material and Methods: We retrospectively analyzed 90 patients with confirmed metastatic GC or GEC, treated with an upfront CT. Inclusion criteria were patients aged ≥75 years, PS 0−2, normal bone marrow/liver/renal function and no major comorbidities. All patients received a G8 score, and some patients with G8 ≤14 received a comprehensive geriatric assessment (CGA). The primary goal was to perform a safety evaluation based on the incidence of adverse events (AE), and the secondary goal was to determine the efficacy (PFS and OS). The chi-square test and the Kaplan−Meier method were used to estimate the outcomes. The statistical significance level was set at p < 0.05. Results: Toxicity rates were quite low: G1/G2 (51.1%) and G3/G4 (25.5%). No toxic deaths were reported. The median PFS was 6.21 months and the median OS 11 months. The G8 score and PS ECOG significantly influenced both PFS and OS. A statistically significant correlation among G8, weight loss, hypoalbuminemia and risk of G3/G4 adverse events was also found. Conclusion: Our research on selected elderly patients did not detect broad differences of efficacy and tolerability compared to a young population. Our study, although retrospective and small-sized, showed that G8 score might be an accurate tool to identify elderly GC/GEC patients who could be safely treated with CT, further recognizing patients who could receive a doublet CT and who may require a single agent chemotherapy or a baseline dose reduction.

Primary versus secondary antiemetic prophylaxis with NK1 receptor antagonists in patients affected by gastrointestinal malignancies and treated with a doublet or triplet combination regimen including oxaliplatin and/or irinotecan plus fluoropyrimidines: A propensity score matched analysis.

Aim: The aim of the current study is to investigate the impact of primary compared to secondary chemotherapy-induced nausea and vomiting (CINV) prophylaxis with NK1 receptor antagonists (NK1-RA) in patients affected by gastrointestinal malignancies and treated with oxaliplatin- and/or irinotecan-based doublet or triplet regimens. Study design and methods: Clinical data of patients affected by gastrointestinal malignancies, treated with an oxaliplatin and/or irinotecan-based doublet or triplet regimen as neo/adjuvant or advanced-line treatment, and who received NK1-RA as primary (from the first cycle of treatment) or secondary (after the onset of CINV with a previous regimen with 5HT3-RA and dexamethasone) prophylaxis for CINV, were retrospectively collected in an observational study involving 16 Italian centers. A propensity score matching was performed by taking into account the following stratification factors: sex (male vs. female), age (< vs. ≥70 years old), overweight (body mass index, BMI < vs. ≥25), underweight (BMI < vs. ≥19), disease spread (early vs. advanced/metastatic), tumor type (esophagogastric cancer vs. the rest, hepatobiliary tumor vs. the rest, colorectal cancer vs. the rest), type of NK1-RA used as primary/secondary prophylaxis (netupitant-palonosetron vs. fosaprepitant/aprepitant), concomitant use of opioids (yes vs. no), concomitant use of antidepressant/antipsychotic drugs (yes vs. no), Eastern Cooperative Oncology Group (ECOG) performance status at the start of NK1-RA treatment (0 vs. 1-2), and intensity of chemotherapy regimen (doublet vs. triplet). Results: Among 409 patients included from January 2015 to January 2022 and eligible for analysis, 284 (69%) and 125 (31%) were treated with NK1-RA as primary and secondary antiemetic prophylaxis, respectively. After matching, primary NK1-RA use was not associated with higher rates of protection from emesis regardless the emesis phase (acute phase, p = 0.34; delayed phase, p = 0.14; overall phase, p = 0.80). On the other hand, a lower rate of relevant nausea (p = 0.02) and need for rescue antiemetic therapy (p = 0.000007) in the overall phase was found in primary NK1-RA users. Furthermore, a higher rate of both complete antiemetic response (p = 0.00001) and complete antiemetic protection (p = 0.00007) in the overall phase was more frequently observed in primary NK1-RA users. Finally, chemotherapy delays (p = 0.000009) and chemotherapy dose reductions (p = 0.0000006) were less frequently observed in primary NK1-RA users. Conclusion: In patients affected by gastrointestinal malignancies, a primary CINV prophylaxis with NK1-RA, 5HT3-RA, and dexamethasone might be appropriate, particularly in those situations at higher risk of emesis and in which it is important to avoid dose delays and/or dose reductions, keeping a proper dose intensity of chemotherapy drugs.