Neo-Adjuvant Treatment in Primary Resectable Pancreatic Cancer: A Systematic Review and PRISMA-Compliant Updated Metanalysis of Oncological Outcomes.

BACKGROUND: Despite advances in treatment, the prognosis of resectable pancreatic adenocarcinoma remains poor. Neoadjuvant therapy (NAT) has gained great interest in hopes of improving survival. However, the results of available studies based on different treatment approaches, such as chemotherapy and chemoradiotherapy, showed contrasting results. The aim of this systematic review and meta-analysis is to clarify the benefit of NAT compared to upfront surgery (US) in primarily resectable pancreatic adenocarcinoma. METHODS: A PRISMA literature review identified 139 studies, of which 15 were finally included in the systematic review and meta-analysis. All data from eligible articles was summarized in a systematic summary and then used for the meta-analysis. Specifically, we used HR for OS and DFS and risk estimates (odds ratios) for the R0 resection rate and the N+ rate. The risk of bias was correctly assessed according to the nature of the studies included. RESULTS: From the pooled HRs, OS for NAT patients was better, with an HR for death of 0.80 (95% CI: 0.72-0.90) at a significance level of less than 1%. In the sub-group analysis, no difference was found between patients treated with chemoradiotherapy or chemotherapy exclusively. The meta-analysis of seven studies that reported DFS for NAT resulted in a pooled HR for progression of 0.66 (95% CI: 0.56-0.79) with a significance level of less than 1%. A significantly lower risk of positive lymph nodes (OR: 0.45; 95% CI: 0.32-0.63) and an improved R0 resection rate (OR: 1.70; 95% CI: 1.23-2.36) were also found in patients treated with NAT, despite high heterogeneity. CONCLUSIONS: NAT is associated with improved survival for patients with resectable pancreatic adenocarcinoma; however, the optimal treatment strategy has yet to be defined, and further studies are required.

Combined response of advanced cutaneous squamous cell carcinoma and renal cell carcinoma to immunotherapy: a case report.

Immune checkpoint inhibitors have significantly improved the therapeutic scenario of many different advanced malignancies and could be an effective treatment strategy in synchronous or metachronous tumors. The authors describe the clinical case of a patient who experienced a long-lasting response of his metastatic renal cell carcinoma and an optimal response of his locally advanced cutaneous squamous cell carcinoma to immunotherapy. The systemic treatment was chosen based on a literature review of several clinical reports, since there was no prospective study on anti-PD-1 blockade activity in cutaneous squamous cell carcinoma when the patient started the treatment. This clinical case supports the growing evidence for immunotherapy as a valid treatment option across different types of advanced tumors.

Immunotherapy is an effective treatment strategy across different cancer types and could be a valid treatment strategy in patients with multiple malignant tumors. In this scenario, in fact, the main challenge is to choose a systemic treatment which could be active on both tumors with an acceptable toxicity profile. The authors report the clinical case of a patient with metastatic renal cell carcinoma and a disfiguring cutaneous cancer of the zygomatic region who experienced a durable response of the renal tumor and almost a complete clinical response of the cutaneous cancer.

Durable response after immunotherapy discontinuation for delayed and severe immune-related adverse events: a case report.

Recent studies have shown that immune-related adverse events (irAEs), occurring even after the discontinuation of immune checkpoint inhibitors (ICIs), may be associated with favorable disease outcomes, particularly in patients with melanoma and lung cancer. However, a few clinical cases have been described on the correlation between irAEs and ICIs efficacy in renal cell carcinoma (RCC) patients. This study reports the clinical case of a metastatic RCC patient who has experienced severe immune-related renal toxicity after 19 months of nivolumab use. Despite immunotherapy discontinuation, the patient has maintained clinical benefit and disease progression-free for 3 years. We examined the correlation between the occurrence and the severity of irAEs, treatment discontinuation and clinical benefits. The evidence on ICI retreatment following ICI discontinuation due to irAEs was also reviewed.

Lay abstract Immunotherapy has profoundly changed the treatment scenario of cancer patients. However, similar to any oncological therapy, it may cause immune-related adverse events. Cancer patients experiencing immune-related adverse events have a higher probability of better survival outcomes. This correlation has been largely described in patients with melanoma and lung cancer, but only a few data have been reported for genitourinary tumor patients. Here, we report the clinical case of a metastatic renal cell carcinoma patient who has experienced a late-onset and severe immune-related renal toxicity after 19 months of immunotherapy, which led to treatment discontinuation. Despite this, the patient has maintained a clinical benefit and disease progression-free for more than 3.5 years. We reviewed the literature on the correlation between immunotherapy benefit and immune-related adverse events, considering the time of onset, the severity of the adverse events and the concepts of treatment discontinuation and retreatment.

Outstanding Response in a Patient With ROS1-Rearranged Inflammatory Myofibroblastic Tumor of Soft Tissues Treated With Crizotinib: Case Report.

Inflammatory myofibroblastic tumor (IMT) is a very rare subtype of sarcoma, which frequently harbor chromosomal rearrangements, including anaplastic lymphoma kinase (ALK) rearrangements (almost 50% of the IMTs) and other kinase fusions such as ROS1. ROS1 fusions are present in about 10% of IMT, almost half of the ALK-negative IMT patients. Apart from radical surgery for resectable tumors, there is no standard-of-care therapy for advanced IMTs. Nonetheless, the use of tyrosine kinase inhibitors has shown promising efficacy in IMT patients with targetable genomic alterations. We report the case of a 24-year-old patient with chemotherapy-refractory metastatic IMT harboring ROS1 kinase fusion, who experienced a significant clinical and pathological response to crizotinib. This clinical case highlights the need to assess all patients with unresectable IMTs for chromosomal abnormalities and gene mutations and address them to targeted agents as well as clinical trials.

The prognostic value of CD3+ tumor-infiltrating lymphocytes for stage II colon cancer according to use of adjuvant chemotherapy: A large single-institution cohort study.

BACKGROUND: High tumor infiltrating lymphocytes (TILs) density was previously shown to be associated with favorable prognosis for patients with colon cancer (CC). However, the impact of TILs on overall survival (OS) of stage II CC patients who received adjuvant chemotherapy (ADJ) or not (no-ADJ) is unknown. We assessed the prognostic value of CD3+ TILs in stage II CC patients according to whether they had ADJ or not. METHODS: Patients treated with curative surgery for stage II CC (2002-2013) were selected from the Santa Maria alle Scotte Hospital registry. TILs at the invasive front, center of tumor, and stroma were determined by immunohistochemistry and manually quantified as the rate of TILs/total tissue areas. High TILs (H-TILs) was defined as >20%. Patients were categorized as high or low TILs (L-TILs) and ADJ or no-ADJ. RESULTS: Of the 678 patients included, 137 (20%) received ADJ and 541 (80%) did not. The distribution of the 4 groups were: 16% (L-TIL/ADJ), 64% (L-TIL/no-ADJ), 5% (H-TIL/ADJ), 15% (H-TIL/no-ADJ). Compared to H-TILs/no-ADJ, ADJ patients showed a significantly increased OS (P<.01) regardless of the TILs rate whereas L-TILs/no-ADJ had significantly decreased OS and higher risk of death (HR=1.41; 95% CI, 1.06-1.88; P<.0001). On multivariable analysis, the unfavorable prognostic value of L-TILs (vs. H-TILs) for no-ADJ patients was confirmed (HR=1.36; 95% CI 1.02, 1.82; P=.0373). CONCLUSION: Low CD3+ TILs rate was associated with shorter OS in those with stage II colon cancer who did not receive adjuvant therapy. Low CD3+ TILs could be considered an additional risk factor for still ADJ-untreated stage II CC patients, which could facilitate clinical decision making.

Adjuvant Chemotherapy for Stage II Colon Cancer.

In stage II colon cancer management, surgery alone has shown a high cure rate (about 80%), and the role of adjuvant chemotherapy is still a matter of debate. Patients with high-risk features (T4, insufficient nodal sampling, grading, etc.) have a poorer prognosis and, usually, adjuvant chemotherapy is recommended. The purpose of the present study is to highlight and discuss what is still unclear and not completely defined from the previous trials regarding risk stratification and therapeutic benefit of adjuvant chemotherapy. With all the limitations of generalizing, we make the effort of trying to quantify the relative contribution of each prognostic factor and the benefit of adjuvant chemotherapy for stage II colon cancer. Finally, we propose a decision algorithm with the aim of summarizing the current evidence and translating it to clinical practice.

Gemcitabine plus nab-paclitaxel followed by maintenance treatment with gemcitabine alone as first-line treatment for older adults with locally advanced or metastatic pancreatic cancer.

OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of the combination Gemcitabine (Gem) plus nab-Paclitaxel (NabP) (Gem/NabP), followed by maintenance Gem in older adults with locally advanced or metastatic pancreatic cancer (PC). MATERIALS AND METHODS: In this prospective observational study, the induction chemotherapy consisted of NabP 125 mg/m2 followed by Gem 1000 mg/m2 on days 1, 8, and 15 of a 4-week cycle. After a maximum of 3 cycles, patients without evidence of progressive disease (PD) were administered Gem 1000 mg/m2 weekly for 3 of 4 weeks as maintenance therapy until documentation of PD or unacceptable toxicity. The primary endpoint was six-month disease-control rate (DCR). RESULTS: Overall, 36 patients >70 years with metastatic or locally advanced PC were enrolled at participating Institutions. After completion of Gem/NabP, 18 (50%) patients achieved partial response, 13 (36%) had stable disease, and 5 (14%) had PD. Thirty-one patients (86%) received Gem monotherapy as maintenance treatment for a median of 3 cycles (range, 2-9 cycles). Six-month DCR was 61% (95% CI, 45-77), median PFS was 6.4 months (95% CI, 5.4-8.3), and median OS was 13.4 months (95% CI, 11.1-16.7). During Gem/NabP regimen, the most common grade 3 toxicity included neutropenia (22%), anemia (19%) and thrombocytopenia (8%). Grade 3 neuropathy was not observed. During Gem maintenance therapy, grade 3 hematological toxicity was described in 6 patients (19%). CONCLUSION: Gem/NabP followed by maintenance Gem appears to be safe and effective for older patients with locally advanced or metastatic PC.