Antonia Strippoli
@policlinicogemelli.it
medical Oncology
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Scopus Publications
Scopus Publications
V. Zurlo, F. Rosa, E. Rinninella, L. Pontolillo, V. Beccia, M. Maratta, G. Tortora, S. Alfieri, C. Pozzo and A. Strippoli
OBJECTIVE
Sarcopenia is a frequent disorder among cancer patients. It commonly leads to muscle mass wasting and poor clinical outcomes, even though it is rarely recognized and often undertreated. The relationship between skeletal muscle depletion and chemotherapy toxicity or postoperative complications is well known. The aim of the present study was to analyze the impact of sarcopenia on clinical outcomes of pretreated metastatic gastric cancer (GC) patients.
PATIENTS AND METHODS
88 pretreated GC patients were retrospectively analyzed. Patients were divided into two groups according to their skeletal mass index (SMI): sarcopenic patients with low SMI (≤39 cm2/m2 for women and ≤55 cm2/m2 for men) and non-sarcopenic patients with normal/high SMI value. The two groups were compared according to outcomes and adverse events.
RESULTS
Progression-free survival (PFS) was significantly higher in patients with normal/high SMI than in those with low SMI (6 vs. 3.5 months, respectively; HR 0.52). Similarly, the overall response rate (ORR) was higher in the subgroup with normal/high SMI (41% vs. 20%; p=0.02). Overall survival (OS) was not significantly different, but multivariate analysis demonstrated that both SMI and performance status were associated with OS. In the sarcopenic group, the patients treated in the second line with paclitaxel and ramucirumab regimen showed a better outcome profile. Overall, adverse events (AEs) were more frequent in the group of patients with low SMI (p<0.0001).
CONCLUSIONS
Early recognition of sarcopenia may contribute to personalizing second or further lines of treatment in advanced GC and to weigh up the potential risk of serious toxicities.
Francesco Santullo, Federica Ferracci, Carlo Abatini, Miriam Attalla El Halabieh, Claudio Lodoli, Giorgio D’Annibale, Ludovica Di Cesare, Luca D’Agostino, Silvia Pecere, Andrea Di Giorgio,et al.
Springer Science and Business Media LLC
Fausto ROSA, Vito LATERZA, Carlo A. SCHENA, Vincenzo TONDOLO, Antonia STRIPPOLI, Marcello COVINO, Giovanni PACINI, Giuseppe QUERO, Claudio FIORILLO, Davide DE SIO,et al.
Edizioni Minerva Medica
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.
Floriana Nappo, Lorenzo Fornaro, Luca Pompella, Silvia Catanese, Daniele Lavacchi, Andrea Spallanzani, Alessandro Cappetta, Marco Puzzoni, Sabina Murgioni, Giulia Barsotti,et al.
Springer Science and Business Media LLC
Abstract 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.
Carlo Alberto Schena, Vito Laterza, Davide De Sio, Giuseppe Quero, Claudio Fiorillo, Gayani Gunawardena, Antonia Strippoli, Vincenzo Tondolo, Nicola de’Angelis, Sergio Alfieri,et al.
MDPI AG
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.
Maurizio Muscaritoli, Alessandra Modena, Matteo Valerio, Paolo Marchetti, Roberto Magarotto, Silvia Quadrini, Filomena Narducci, Giuseppe Tonini, Teresa Grassani, Luigi Cavanna,et al.
MDPI AG
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, 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.
Fausto Rosa, Carlo Alberto Schena, Vito Laterza, Giuseppe Quero, Claudio Fiorillo, Antonia Strippoli, Carmelo Pozzo, Valerio Papa, and Sergio Alfieri
MDPI AG
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.
Ina Valeria Zurlo, Carmelo Pozzo, Antonia Strippoli, Samantha Mignogna, Michele Basso, Raffaella Vivolo, Giovanni Trovato, Michele Ciaburri, Franco Morelli, Emilio Bria,et al.
MDPI AG
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.
Alessandro Parisi, Riccardo Giampieri, Alex Mammarella, Cristiano Felicetti, Lisa Salvatore, Maria Bensi, Maria Grazia Maratta, Antonia Strippoli, Roberto Filippi, Maria Antonietta Satolli,et al.
Frontiers Media SA
AimThe 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 methodsClinical 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 (&lt; vs. ≥70 years old), overweight (body mass index, BMI &lt; vs. ≥25), underweight (BMI &lt; 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).ResultsAmong 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.ConclusionIn 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.
Fausto Rosa, Fabio Longo, Carmelo Pozzo, Antonia Strippoli, Giuseppe Quero, Claudio Fiorillo, Maria Cristina Mele, and Sergio Alfieri
Elsevier BV
Ina Valeria Zurlo, Mattia Schino, Antonia Strippoli, Maria Alessandra Calegari, Alessandra Cocomazzi, Alessandra Cassano, Carmelo Pozzo, Mariantonietta Di Salvatore, Riccardo Ricci, Carlo Barone,et al.
Springer Science and Business Media LLC
AbstractThe 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.
Elisa Giommoni, Daniele Lavacchi, Giuseppe Tirino, Lorenzo Fornaro, Francesco Iachetta, Carmelo Pozzo, Maria Antonietta Satolli, Andrea Spallanzani, Marco Puzzoni, Silvia Stragliotto,et al.
Springer Science and Business Media LLC
Abstract 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.
Elena Rodolfino, Margo’ Di Marco, Alessia Ilot, Roberto Iezzi, Benedetta Gui, Giacomo Avesani, Camilla Panico, Antonia Strippoli, Andrea Di Giorgio, Fabio Pacelli,et al.
MDPI AG
Peritoneal carcinomatosis frequently occurs in advanced gastrointestinal and gynecological cancers. As factors such as poor drug uptake and distribution cause chemotherapy to be less effective, alternative therapies have been explored. Introduced in 2013, PIPAC (pressurized intraperitoneal aerosol chemotherapy) uses aerosolized chemotherapeutics sprayed into the patient’s peritoneal cavity using a laparoscopic approach. Despite the literature showing encouraging data regarding the tolerability and efficacy of PIPAC, there is a lack of articles on the role that imaging plays in selecting patients suitable for PIPAC. The aim of this study is to combine literature-based evidence and clinical experience to provide information able to support training radiologists, as well as experienced radiologists interested in innovative therapies.
Emanuele Rinninella, Marco Cintoni, Pauline Raoul, Francesca Romana Ponziani, Maurizio Pompili, Carmelo Pozzo, Antonia Strippoli, Emilio Bria, Giampaolo Tortora, Antonio Gasbarrini,et al.
Springer Science and Business Media LLC
AbstractLow muscle mass has been associated with worse clinical outcomes in various cancers. This work investigated whether, during tyrosine kinases inhibitors (TKIs) therapy, low muscle mass was associated with treatment toxicity and survival outcomes. A systematic literature search was performed in Pubmed, Web of Science, and Scopus databases from inception to June 2020, based on fixed inclusion and exclusion criteria. Effect sizes were estimated with hazard ratios (HR) and odds ratios (OR) with 95% confidence interval (CI) and heterogeneity was assessed by measuring inconsistency (I2) based on the Chi squared test. A total of 24 retrospective studies were identified, enrolling patients treated with sorafenib (n = 12), sunitinib (n = 6), lenvatinib (n = 3), regorafenib (n = 2), gefitinib (n = 1), imatinib (n = 1), and pazopanib (n = 1). Thirteen studies were deemed eligible for pooled analyses. Meta-analyses found a significant effect of low muscle mass on dose-limiting toxicity (DLT) (OR 2.40, 95% CI 1.26–4.58, p = 0.008, I2 = 51%) in patients treated with TKI therapy. A subgroup analysis by treatment showed an association between DLT and low muscle during sorafenib or sunitinib, although not significant. A significant association between low skeletal muscle index and poorer overall survival was observed in HCC patients treated with sorafenib (HR 1.45, 95% CI 1.07–1.96, p = 0.02). For other TKIs, although some results showed an association between low muscle mass and worse outcomes, the number of studies for each TKI therapy was too small to reach conclusions. Skeletal muscle mass could influence the prognosis of some TKI-treated patients. This effect is demonstrated in sorafenib-treated HCC patients but remains almost unexplored in other cancer patients undergoing TKI therapy. Further prospective studies with large sample size and sufficient follow-up are needed to clarify the role of muscle mass in the metabolism of TKI-based cancer treatment, and its association with toxicity and survival.
Alessandra Raimondi, Federica Palermo, Michele Prisciandaro, Massimo Aglietta, Lorenzo Antonuzzo, Giuseppe Aprile, Rossana Berardi, Giovanni G. Cardellino, Giovanni De Manzoni, Ferdinando De Vita,et al.
MDPI AG
In resectable gastric or gastroesophageal junction cancer (GC/GEJC), the powerful positive prognostic effect and the potential predictive value for a lack of benefit from the combination of adjuvant/peri-operative chemotherapy for the MSI-high status was demonstrated. Given the high sensitivity of MSI-high tumors for immunotherapy, exploratory trials showed that combination immunotherapy induces a high rate of complete pathological response (pCR), potentially achieving cancer cure without surgery. INFINITY is an ongoing phase II, multicentre, single-arm, multi-cohort trial investigating the activity and safety of tremelimumab and durvalumab as neoadjuvant (Cohort 1) or potentially definitive (Cohort 2) treatment for MSI-high/dMMR/EBV-negative, resectable GC/GEJC. About 310 patients will be pre-screened, to enroll a total of 31 patients, 18 and 13 in Cohort 1 and 2, at 25 Italian Centres. The primary endpoint of Cohort 1 is rate of pCR (ypT0N0) and negative ctDNA after neoadjuvant immunotherapy, of Cohort 2 is 2-year complete response rate, defined as absence of macroscopic or microscopic residual disease (locally/regionally/distantly) at radiological examinations, tissue and liquid biopsy, during non-operative management without salvage gastrectomy. The ongoing INFINITY proof-of-concept study may provide evidence on immunotherapy and the potential omission of surgery in localized/locally advanced GC/GEJC patients selected for dMMR/MSI-high status eligible for radical resection.
Carlo Barone, Maria Di Bartolomeo, Sara Lonardi, Evaristo Maiello, Erika Martinelli, Roberto Moretto, Antonia Strippoli, Emiliano Tamburini, Alberto Zaniboni, and Carmine Pinto
Future Medicine Ltd
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.
Emanuele Rinninella, Antonia Strippoli, Marco Cintoni, Pauline Raoul, Raffaella Vivolo, Mariantonietta Di Salvatore, Enza Genco, Riccardo Manfredi, Emilio Bria, Giampaolo Tortora,et al.
MDPI AG
Background: The impact of the new chemotherapy, fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) on body composition in gastric cancer (GC) patients remains unknown. We assessed body composition changes of GC patients receiving the FLOT regimen and their impact on treatment outcomes. Methods: Preoperative pre- and post-FLOT computed tomography (CT) scans of advanced GC patients were studied. Lumbar skeletal muscle index (SMI) and adipose indices were calculated before and after FLOT. Results: A total of 26 patients were identified between April 2019 and January 2020. Nineteen patients were sarcopenic at diagnosis. The mean BMI decreased (from 24.4 ± 3.7 to 22.6 ± 3.1; p < 0.0001) as well as the SMI (from 48.74 ± 9.76 to 46.52 ± 9.98; p = 0.009) and visceral adipose index (VAI) (from 49.04 ± 31.06 to 41.99 ± 23.91; p = 0.004) during preoperative FLOT therapy. BMI, SMI, and VAI variations were not associated with toxicity, Response Evaluation Criteria in Solid Tumors (RECIST), response, delay and completion of perioperative FLOT chemotherapy, and the execution of gastrectomy; a decrease of SMI ≥ 5% was associated with a higher Mandard tumor regression grade (p = 0.01). Conclusions: Almost three-quarters (73.1%) of GC patients were sarcopenic at diagnosis. Preoperative FLOT was associated with a further reduction in SMI, BMI, and VAI. These changes were not associated with short-term outcomes.
Michele Basso, Salvatore Corallo, Maria Alessandra Calegari, Ina Valeria Zurlo, Francesco Ardito, Maria Vellone, Silvio Marchesani, Armando Orlandi, Vincenzo Dadduzio, Giovanni Fucà,et al.
Springer Science and Business Media LLC
Hepatic resection is the gold standard treatment for patients affected by liver-limited colorectal metastases. Reports addressing the impact of multidisciplinary team (MDT) evaluation on survival are controversial. The aim of this study was to evaluate the benefit of MDT management in these patients in our Institution experience. The objective of the analysis was to compare survivals of patients managed within our MDT (MDT cohort) to those of patients referred to surgery from other hospitals without MDT discussion (non-MDT cohort). Of the 523 patients, 229 were included in the MDT cohort and 294 in the non-MDT cohort. No difference between the two groups was found in terms of median overall survival (52.5 vs 53.6 months; HR 1.13; 95% CI, 0.88–1.45; p = 0.344). In the MDT cohort there was a higher number of metastases (4.5 vs 2.7; p < 0.0001). The median duration of chemotherapy was lower in MDT patients (8 vs 10 cycles; p < 0.001). Post-operative morbidity was lower in the MDT cohort (6.2 vs 21.5%; p < 0.001). One hundred and ninety-seven patients in each group were matched by propensity score and no significant difference was observed between the two groups in terms of OS and DFS. Our study does not demonstrate a survival benefit from MDT management, but it allows surgery to patients with a more advanced disease. MDT assessment reduces the median duration of chemotherapy and post-operative morbidities.
Emanuele Rinninella, Marco Cintoni, Pauline Raoul, Carmelo Pozzo, Antonia Strippoli, Francesca Romana Ponziani, Maurizio Pompili, Emilio Bria, Giampaolo Tortora, Antonio Gasbarrini,et al.
MDPI AG
In cancer patients, loss of muscle mass is significantly associated with low tolerability of chemotherapy and poor survival. Despite the great strides in the treatment of cancer, targeted therapies such as tyrosine kinase inhibitors (TKIs) could exacerbate muscle wasting. Over recent years, the impact of skeletal muscle loss during TKI therapy on clinical outcomes has been in the spotlight. In this review, we focus on the different molecular pathways of TKIs potentially involved in muscle wasting. Then, we report the results of the studies assessing the effects of different TKI therapies—such as sorafenib, regorafenib, sunitinib, and lenvatinib—on muscle mass, and highlight their potential clinical implications. Finally, we discuss an integrative nutritional approach to be adopted during TKI treatment. The assessment of muscle mass from computerized tomography imaging could be helpful in predicting toxicity and prognosis in patients treated with TKI such as sorafenib. Early recognition of low muscle mass and effective personalized nutritional support could prevent or attenuate muscle mass wasting. However, the role of nutrition is still overlooked, and future clinical trials are needed to find the optimal nutritional support to countermeasure muscle mass depletion during TKI therapy.
Andrea Di Giorgio, Carlo Alberto Schena, Miriam Attalla El Halabieh, Carlo Abatini, Emanuele Vita, Antonia Strippoli, Frediano Inzani, Elena Rodolfino, Bruno Romanò, Fabio Pacelli,et al.
Elsevier BV
BACKGROUND
Few patients affected by gastric cancer peritoneal metastasis (GCPM) are offered locoregional treatment, despite several proof-of-efficacy trials. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has emerged in recent years as a promising tool to control peritoneal carcinomatosis. The combination of PIPAC with systemic chemotherapy may offer a greater clinical benefit than standard treatment alone.
METHODS
A single-center cohort of 28 consecutive patients affected by GCPM was scheduled for bidirectional treatment, comprising PIPAC and systemic chemotherapy, from September 2017 to September 2019. Data recorded included safety, efficacy and survival outcomes. Ascite volumes, the Peritoneal Cancer Index (PCI) and pathological response through the Peritoneal Regression Grading Score (PRGS) were compared in those patients who underwent more than one PIPAC procedure.
RESULTS
Forty-six PIPAC procedures were administered, with a mean of 1.7 PIPAC procedures per patient. The median time to resume systemic chemotherapy after PIPAC was 6 days (range 4-7). Concerning safety, two grade 3-4 CTCAE (Common Terminology Criteria for Adverse Events v4.0) toxicity events and one intraoperative complication were recorded. Thirteen patients repeated PIPAC. A pathological response was recorded in 61.5% of patients (one with complete and seven with partial regression). The median overall survival was 12.3 months in the overall population and 15.0 months in patients undergoing more than one PIPAC procedure.
CONCLUSIONS
A bidirectional approach for GCPM was feasible and safe, as the PIPAC procedure integrates well with several systemic chemotherapy regimens. The pathological response demonstrated the antitumoral efficacy of PIPAC. The proposed bidirectional approach may be further investigated in the first-line treatment of metastatic gastric cancer.
Emanuele Rinninella, Marco Cintoni, Pauline Raoul, Carmelo Pozzo, Antonia Strippoli, Emilio Bria, Giampaolo Tortora, Antonio Gasbarrini, and Maria Cristina Mele
Elsevier BV
BACKGROUND & AIMS
Nutritional interventions may improve quality of life, morbidity and mortality in gastric cancer (GC) patients. A growing number of randomized controlled trials (RCTs) evaluated different nutritional strategies - oral nutritional supplements (ONS), enteral nutrition (EN), enteral immunonutrition (EIN), parenteral nutrition (PN) and nutritional counselling - in GC patients. This systematic review and meta-analysis aims to assess the effects of these nutritional interventions on nutritional status of GC patients undergoing gastrectomy and/or chemotherapy.
METHODS
A systematic literature search was performed in Pubmed, Web of Science and Scopus databases from inception to March 2020, based on fixed inclusion and exclusion criteria. Effect sizes were estimated with mean difference (MD) or standard mean difference (SMD) with 95% confidence interval (CI) and heterogeneity was assessed by measuring inconsistency (I2) based on chi-squared test. Pooled analyses and quality assessment were performed with Review Manager 5.3.
RESULTS
A total of 25 RCTs were identified, including ONS (n = 7), EN (n = 6), PN (n = 4), EIN (n = 5) and nutrition counselling (n = 3) interventions. Ten RCTs with 1838 patients were deemed eligible for pooled analyses. Body weight loss was found lower in ONS group versus control group (MD 0.77; 95% CI -0.02-1.56; p = 0.05). PN and EIN studies did not assess body weight, while all nutrition counselling studies did not show significant differences (p > 0.05). Twenty-three out of 25 studies evaluated serum protein levels - albumin (ALB) and/or prealbumin (PA) and/or transferrin (TF). ALB levels did not significantly differ (p > 0.05) in 4 ONS studies. Significant improvements of PA levels from baseline to postoperative day (POD) ≥ 7 were shown in EN compared with PN groups (MD 19.90; 95% CI 10.09-29.70; p < 0.0001). Compared with EN, EIN interventions showed no significant improvements of ALB, PA and TF levels (p > 0.05) from baseline to POD ≥ 7. Amino-acid enriched PN showed no significant improvements of ALB, PA and TF levels (p > 0.05) while the effect of omega-3 enriched PN was debated. Only three studies out of 25 evaluated total fat mass and skeletal muscle mass and no significant differences (p > 0.05) were found between ONS versus control groups.
CONCLUSIONS
Whereas our meta-analysis showed promising results from ONS and EN interventions the optimal delivery of GC nutritional support and nutritional status assessment are still unclear. Moreover, the majority of studies did not consider muscle mass and strength as nutritional parameters. This review highlights the crucial need to close this research gap, with high-quality, large RCTs, adopting effective nutritional assessment tools to evaluate the appropriateness of nutrition strategies.
Annamaria Agnes, Alberto Biondi, Antonio Laurino, Antonia Strippoli, Riccardo Ricci, Carmelo Pozzo, Roberto Persiani, and Domenico D'Ugo
Wiley
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.
Emanuele Rinninella, Marco Cintoni, Pauline Raoul, Carmelo Pozzo, Antonia Strippoli, Emilio Bria, Giampaolo Tortora, Antonio Gasbarrini, and Maria Cristina Mele
Elsevier BV
BACKGROUND & AIMS
Computed tomographic (CT) imaging at third lumbar vertebra (L3), routinely used by oncologists, represents a reliable tool to quantify muscle mass. A systematic review and meta-analysis was performed to assess the efficacy of CT scan to define muscle mass as a prognostic marker in gastric cancer (GC) patients undergoing gastrectomy and/or chemotherapy. The primary outcomes were overall survival (OS) and recurrence-free survival (RFS) and the secondary outcomes included postoperative length of hospital stay (P-LOS), total and severe complications in GC patients undergoing gastrectomy.
METHODS
Three electronic bibliographic databases - MEDLINE, Web of Science and Cochrane Central Register of Controlled Trials - were used to conduct a systematic literature search based on fixed inclusion and exclusion criteria, until April 2019. The adjusted and unadjusted hazard ratio (HR), odds ratio (OR) and mean difference (MD) with 95% confidence interval (CI) were used to analyse the dichotomous variables (OS, RFS, total and severe complications) and continuous variables (P-LOS). Random- and fixed effects models were used according to the heterogeneity.
RESULTS
A total of 5610 GC patients from 20 studies were identified. Low muscle mass at diagnosis was found in 32.7% of GC patients and was significantly associated with poorer OS (HR 2.02, 95% CI 1.71-2.38, p < 0.00001, I2 = 47%) and worse RFS (HR 1.97, 95% CI 1.71-2.26, p < 0.00001, I2 = 0%). Meta-analysis of adjusted HR from multivariable analyses confirmed the association between OS and low muscle mass (HR 1.89, 95% CI 1.68-2.12, p < 0.00001, I2 = 36%). Furthermore, low muscle mass and poorer OS were significantly associated in metastatic GC patients exclusively undergoing chemotherapy (HR 1.61, 95% CI 1.23-2.11, p < 0.0006, I2 = 18%). Moreover, preoperative low muscle mass was significantly associated with longer P-LOS (MD 1.19, 95% CI 0.68-1.71, p < 0.00001, I2 = 0%), higher risk of postoperative complications (OR 1.76, 95% CI 1.17-2.66, p = 0.007, I2 = 77%) and severe complications (OR 1.54, 95% CI 1.03-2.29, p = 0.04, I2 = 49%) in GC patients undergoing gastrectomy.
CONCLUSIONS
Low muscle mass, assessed by L3 CT-scan, affects almost 1/3 of GC patients at diagnosis and acts as a negative prognostic marker on many clinical outcomes. Therefore, identifying GC patients with low muscle mass at diagnosis or at follow-up visit should be recommendable. Clinical nutritionists should be part of tumor boards meetings to screen low muscle mass in order to prompt personalized nutritional support.
Antonia Strippoli, Alessandra Cocomazzi, Michele Basso, Tonia Cenci, Riccardo Ricci, Francesco Pierconti, Alessandra Cassano, Vincenzo Fiorentino, Carlo Barone, Emilio Bria,et al.
MDPI AG
Alterations in the transcriptional factor c-MYC could be involved in the anti-EGFR resistance in metastatic colorectal cancer (mCRC). The c-MYC expression was evaluated in 121 RAS and BRAF wild-type mCRC before treatment with anti-EGFR+Folfiri therapy and in 33 subsequent metastases collected during target therapy (TT) or in TT resistance phase. We analyzed the expression and the functional role of some c-MYC linked miRNAs (miR-31-3p, miR-143 and miR-145) in our patient group and in two CRC cell lines, also performing a c-MYC target PCR array. Patients with higher c-MYC expression (HME) showed a significant lower PFS and OS when compared to those with low c-MYC expression (LME). HME pattern was significantly more frequent in the metastases after TT and significantly associated to anti-EGFR molecular resistance alterations. We also found a significant correlation between the expression of the above-mentioned c-MYC linked miRNAs, c-MYC level and anti-EGFR resistance. Moreover, expression gene profiling pointed out the pivotal role of c-MYC in CRC-related cell-cycle, apoptosis, signal transduction and cell-growth pathways. c-MYC expression might distinguish patients with a lower PFS and OS in anti-EGFR treated mCRC. The individuation of some miRNAs involved in the c-MYC pathway regulation and the downstream c-MYC effector genes could provide a new possible target to overcome the anti-EGFR resistance in mCRC.
Ina Valeria Zurlo, Michele Basso, Antonia Strippoli, Maria Alessandra Calegari, Armando Orlandi, Alessandra Cassano, Mariantonietta Di Salvatore, Giovanna Garufi, Emilio Bria, Giampaolo Tortora,et al.
MDPI AG
Background: Guidelines recommend a perioperative approach in patients with stage II/III gastric cancer, but in real-life many patients receive immediate surgery followed by adjuvant chemotherapy (aCT). Although histologic subtypes may have different response to CT, no study has explored the influence of histotype on the efficacy of perioperative CT (pCT) or aCT. Materials and methods: The objective of the study was to evaluate the impact of clinicopathological features and histology (intestinal or diffuse) on survival according to strategy (pCT vs. aCT). The primary endpoint was overall survival (OS) and the secondary endpoint was event-free survival (EFS). Results: Out of 203 patients affected by LAGC, 83 received pCT and 120 aCT. At multivariate, histology and LVI in pCT cohort and positive resection margin in the aCT influenced both OS and EFS. No difference in EFS and OS was observed in relation to strategy. However, in the intestinal-type of pCT cohort survival outcomes were significantly higher compared to the aCT cohort, whereas in the diffuse-type were significantly worse in patients receiving pCT compared to those receiving aCT. Conclusions: Although retrospective and small-sized, this study suggests that the benefit of pCT might be limited to the intestinal-type. This hypothesis needs to be confirmed in prospective series.