Radiomics to predict immunotherapy efficacy in advanced renal cell carcinoma: A retrospective study

Immunotherapy has become a cornerstone for the treatment of renal cell carcinoma. Nevertheless, some patients are resistant to immune checkpoint inhibitors. The possibility to identify patients who cannot benefit from immunotherapy is a relevant clinical challenge. We analyzed the association between several radiomics features and response to immunotherapy in 53 patients treated with checkpoint inhibitors for advanced renal cell carcinoma. We found that the following features are associated with progression of disease as best tumor response: F_stat.range (p < .0004), F_stat.max (p < .0007), F_stat.var (p < .0016), F_stat.uniformity (p < .0020), F_stat.90thpercentile (p < .0050). Gross tumor volumes characterized by high values of F_stat.var and F_stat.max (greater than 60,000 and greater than 300, respectively) are most likely related to a high risk of progression. Further analyses are warranted to confirm these results. Radiomics, together with other potential predictive factors, such as gut microbiota, genetic features or circulating immune molecules, could allow a personalized treatment for patients with advanced renal cell carcinoma

Current evidence for second-line treatment in metastatic renal cell carcinoma after progression to immune-based combinations

The recent approval of immune checkpoint inhibitor (ICI)-based combinations has redefined the first-line standard of care of metastatic renal cell carcinoma (mRCC) patients. Although the undisputed advantage of these combinations, most patients progressed, requiring subsequent therapies. The change of first-line therapy inevitably led to modification of the all mRCC treatment algorithm; to date, the most appropriate second-line options remain still unclear. The aim of our review was to provide a useful summary of the available evidence in order to overcome the doubts about treatment sequences. Retrospectively, the efficacy of second-line VEGFR-TKIs seems to be greater after failure of a dual ICIs combination rather than after ICIs plus VEGFR-TKIs, nevertheless prospective data of second-line TKIs are limited. Moreover, ICI re-challenge could be an option but, again, most data derived from retrospective series emphasizing the identification of predictive factors of response to select mRCC patients that could benefit from this strategy. Novel molecules and different ICI-based combinations are under evaluation with the aim of implementing the second-line setting. In particular, belzutifan, ciforadenant (CPI-444), and talazoparib achieved encouraging objective response rates (ORR) in phase I/II trials. Phase III trials comparing these new molecules with the standard of care are currently ongoing. The first-line regimen, and the type and duration of response emerged as crucial factors that could influence the efficacy of second-line therapy. Prognostic models that integrate clinical features and molecular biomarkers with a predictive value are warranted to guide clinicians in the decision-making process with the ultimate goal of offering to the patients the most effective therapy in a personalized, precision medicine-based, therapeutic strategy

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

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 (= 70 years old), overweight (body mass index, BMI = 25), underweight (BMI = 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

Pancreas as an Unusual Metastatic Site of Medullary Thyroid Carcinoma: A Case of Very Long-term Follow-up Under Prolonged Treatment with Somatostatin Analogues

Background: Pancreatic metastases from medullary thyroid carcinoma (MTC) are exceptional. Imaging and treatment based on somatostatin receptors may play a role, though the evidence is unconvincing. Case presentation: We have, herein, documented a unique case of metastatic MTC, where pancreatic metastasis was identified by 68Ga-PET/CT, with the disease showing very slow progression during treatment with lanreotide autogel. A 51-year-old woman underwent total thyroidectomy for goiter in 2000, with a postoperative diagnosis of MTC. Due to persistent disease, somatostatin analogues (SSA) treatment commenced in 2005, following a positive acute octreotide test. In 2012, a pathology-confirmed pancreatic metastasis was diagnosed via 68Gallium-positron emission tomography (68Ga-PET/CT). The disease progressed very slowly over 17 years of SSA treatment. Conclusion: This uncommon case of pancreatic metastasis from MTC indicates that nuclear medicine techniques might offer valuable additional information. Extended treatment with lanreotide autogel appears to correlate with very slow disease progression in selected patients