Immune checkpoint inhibitor doublets: Are they beneficial for older patients? A systematic review and meta-analysis.

INTRODUCTION: The introduction of immune checkpoint inhibitors (ICIs) has significantly transformed the treatment landscape for advanced malignancies. These inhibitors bolster the immune system's capacity to detect and destroy cancer cells. ICIs used in cancer immunotherapy are primarily categorized into two groups: anti-PD-1/L1 and anti-CTLA-4. The application of combination ICI therapy (ICI doublets) in older patients prompts questions about their relative efficacy compared to standard therapies, particularly in comparison to younger patient cohorts. MATERIALS AND METHODS: This study involved an extensive review of literature from databases including PubMed, Embase, and the Cochrane Register of Controlled Trials. Our primary aim was to assess overall survival (OS) outcomes in a cohort of older patients, specifically those aged 65 and above, undergoing treatment for advanced cancers. The treatment modalities considered included ICI doublets, ICI monotherapy (alone or in combination with non-ICI drugs), and non-ICI therapies. The study aimed to compare the OS outcomes across these different therapeutic approaches. RESULTS: The analysis incorporated data from 18 trials, indicating that patients treated with ICI doublets exhibited a statistically significant improvement in OS compared to the control group (hazard ratio [HR] = 0.9, 95% confidence interval [CI] 0.84-0.96; P < 0.01). The addition of CTLA-4 inhibitors did not show significant advantages over anti-PD-1/L1 monotherapy (HR = 0.92, 95% CI 0.83-1.02; P = 0.13). When compared to non-ICI therapies, such as chemotherapy alone, ICI doublets demonstrated improved OS outcomes (HR = 0.89, 95% CI 0.82-0.97; P < 0.01). DISCUSSION: Our findings suggest that ICI doublets may offer a modest improvement in the outcomes of older cancer patients compared to non-ICI-based treatments. Consequently, the use of ICI doublets in older patients should be considered on an individual basis, prioritizing cases where there are clear advantages over conventional therapy. This study underscores the importance of developing personalized treatment strategies for older patients, necessitating a cautious and individualized approach in medication selection.

Gonadal vein leiomyosarcoma, from clinical practice to a literature review: surgical, oncological and histopathologic correlation.

BACKGROUND AND AIM: Vascular leiomyosarcomas are rare and generally originate from the muscular wall of the inferior vena cava. Leiomyosarcomas originating from the wall of the gonadal veins are rare and just about ten cases are described in literature. In the present paper, we have described a case of a LMS originating from the left gonadal vein. METHODS: A 44-year-old woman presented in March 2020 pain symptoms at the level of the left renal lodge. The subsequent CT and the biopsy confirmed the diagnosis of G2 grade LMS. The mass was then removed en bloc from the posterior and inferior pancreatic plane, from the aortic plane and from the retroperitoneal plane, post chemoteraphy. RESULTS: Pathologic report revealed a typical leiomyosarcoma, moderately differentiated G2 with minor dedifferentiated areas of pleomorphic leiomyosarcoma. CONCLUSIONS: The LMSs originating from gonadal veins represent an uncommon oncologic challenge. The radical en bloc excision represents the therapeutic gold standard.

Maintenance in gastric cancer: New life for an old issue?

The interest in maintenance therapy for patients with advanced cancers has been rapidly growing. Maintenance therapy is a useful strategy that may strengthen results of induction therapy thus extending survival and preserving the quality of life (QoL) with less toxicity. Maintenance also represents a suitable setting to investigate novel agents. The value of maintenance therapy after first-line chemotherapy has been well established in several solid tumours, such as colorectal, lung, breast, and ovarian cancer in which it is largely adopted. To date, there is no established role for maintenance therapy following first-line chemotherapy for advanced gastric cancer (GC). This review summarizes the current knowledge regarding maintenance strategies in advanced GC exploring cytotoxic agents, biologic agents and immunotherapy. We also critically review new issues to optimize randomized clinical trials for maintenance therapies and suggest clinical consideration to guide a personalized approach in daily clinical practice for this setting.

The role of Geriatric screening tool (G8) in predicting side effect in older patients during therapy with aromatase inhibitor.

BACKGROUND: Endocrine therapy is the main treatment in hormonosensitive breast cancer; the most frequent side effects are arthralgia, osteoporosis, depression, dyslipidemia and hypertension. G8 is a simple test developed to identify older patients who could benefit from a comprehensive geriatric assessment (CGA). The aim of this study is to evaluate the possible role of G8 in predicting side effects from treatment with aromatase inhibitor in women ≥65 years old. MATHERIAL AND METHOD: Women ≥65 years old affected by breast cancer about to start a therapy with an aromatase inhibitor, in the adjuvant setting, were evaluated with the G8 tool. Patients were classified as "fit" with G8 score > 14 or "vulnerable" with G8 score ≤ 14; they then started treatment and clinical-instrumentalfollow-up. RESULTS: From April 2016 to February 2018, 50 consecutive patients were screened. Median age was 75.1 (range 65-86). G8 identified 30 patients (60%) as "fit" (score > 14) and 20 (40%) as "vulnerable" (score ≤ 14). The grade of concordance between G8 score and the appearance/absence of adverse events were statistically significant (41/50 patients, 82%, p = 0.0002); sensitivity resulted in 78% and specificity was 81%; positive predictive value was 70% and negative predictive value was 87%. The most frequent adverse event was arthromyalgia. CONCLUSION: The G8 screening tool has a potential role in predicting side effects during a treatment with aromatase inhibitor. G8 could be very useful in everyday clinical practice for this population.

Case report of a 65-year-old man with biatrial metastatic localisation from poorly differentiated cutaneous squamous cell carcinoma.

We report the case of an immunocompetent 65-year-old man affected by cutaneous squamous cell carcinoma (cSCC) with lung and biatrial metastatic localisation. In May 2018, the patient underwent lower limb amputation due to the finding of a large ulceration which upon biopsy was found to be a poorly differentiated squamous cell carcinoma (SCC), ulcerated, full-thickness infiltrating from the skin to the underlying bone tissue. After 1 month, a radiological restaging found multiple pulmonary localisations and a right-atrial metastatic localisation. The patient was then studied in-depth and a transesophageal echocardiogram found that the patient had two 2 and 5 cm metastatic localisations in the left atrium and a 3-cm metastatic localisation in the right atrium. Informed about the clinical situation and about the risks of a chemotherapeutic treatment, the patient decided not to start any treatment. This case represents, to our knowledge, the only case of a biatrial metastatic localisation from cSCC and is representative of how cardiac symptoms and signs in patients affected by this disease must be evaluated.

Long-Lasting Exceptional Radiological Complete Response after Treatment with Eribulin in a Patient with Triple-Negative Breast Cancer with Liver Involvement.

We report the case of a 50-year-old woman with a triple-negative Ki67 80% breast cancer with liver metastases, who obtained a radiological long-lasting complete response after treatment with eribulin. The patient initially experienced progressive disease after a standard anthracycline/taxane-based adjuvant chemotherapy, a first-line treatment for metastatic disease with paclitaxel-bevacizumab, and a second-line maintenance treatment with bevacizumab and capecitabine. Eribulin was administered according to a 1.23 mg/m2 scheme on days 1 and 8 every 3 weeks, and the treatment was always well tolerated. After 45 cycles of therapy, we still detected radiological evidence of complete response on liver sites of disease. This case report underlines the great efficacy of eribulin as third-line treatment for metastatic disease in a very aggressive form of breast cancer.

Everolimus in Combination with Octreotide Long-Acting Repeatable in a First-Line Setting for Patients with Neuroendocrine Tumors: A 5-Year Update.

BACKGROUND: We previously presented data of this multicentric, phase II study showing that everolimus plus octreotide long-acting repeatable (LAR) for advanced neuroendocrine neoplasms (NENs), in the first line setting, is an active and safe treatment. We now present updated data at 5 years. METHODS: Patients with advanced well-differentiated, previously untreated neuroendocrine tumors of the gastroenteropancreatic tract and of the lung received octreotide LAR 30 mg plus everolimus 10 mg/day. The primary endpoint was the objective response rate (ORR). We performed an analysis of "long responder" patients and of time to progression (TTP) and overall survival (OS) at 5 years. RESULTS: Fifty patients were enrolled; the primary tumor site was: pancreas (14 patients), lung (11 patients), ileum (9 patients), jejunum/duodenum (2 patients), and unknown (14 patients). Seventeen (34%) of these patients have received treatment for more than 2 years. The median exposure to study drugs was 519.5 days (range 48-2,024). Currently 3 patients are still in treatment. The ORR (partial response + complete response) was 18% (95% confidence interval [CI] 7.4-28.6): complete response 1 patient (2%), partial response 8 patients (16%), stable disease 37 patients (74%). The median TTP was 33.6 months (95% CI 18.7-41.2) and the median OS was 61.0 months (95% CI 49.8-not reached). CONCLUSION: In this update of clinical outcome at 5-year follow-up, everolimus plus octreotide has been shown to be active in advanced NENs. The current analysis showed a further prolongation of TTP and a long exposure to the study drug without major side effects in the long term.

Carboplatin-Paclitaxel versus Cisplatin-Ifosfamide in the treatment of uterine carcinosarcoma: a retrospective cohort study.

OBJECTIVE: Uterine carcinosarcoma (CS) is a rare neoplasm whose adjuvant treatment has not been yet defined. We report on the activity and toxicity of cisplatin-ifosfamide and carboplatin-paclitaxel as adjuvant treatments for patients with uterine CS. METHODS: Data of International Federation of Gynecology and Obstetrics (FIGO) stage I to IV uterine CS patients treated between 2006 and 2012 with adjuvant chemotherapy (cisplatin 20 mg/mq and ifosfamide 1500 mg/mq day 1 to 4 every 3 weeks plus prophylactic Granulocyte colony-stimulating factor (G-CSF) support [group A] or carboplatin area under the curve -5 (AUC-5) and paclitaxel 175 mg/mq d1q21 [group B]) were retrospectively reviewed. Progression-free survival, overall survival, and chemotherapy-related toxicities were compared between the 2 groups. A subanalysis of oncologic outcomes according to the sarcomatous component (homologous vs heterologous) was performed. RESULTS: Forty-six women were evaluated-21 in group A and 25 in group B. At a median follow-up of 30 months, the median progression-free survival was 11.6 months (95% confidence interval [CI], 6.3-16.9) and 16.6 months (95% CI, 14.7-18.5) for group A and B, respectively (P = 0.20). The median overall survival was 17.1 months (95% CI, 12.6-21.5) and 35.1 months (95% CI, 26.3-43.7) for group A and B, respectively (P = 0.14). No differences were identified among heterologous or homologous components according to chemotherapy treatment. Toxicity profiles widely differ between treatment arms. CONCLUSIONS: Because of the super imposable activity and the better toxicity profile, carboplatin-paclitaxel may be a suitable alternative to cisplatin-ifosfamide in the treatment of uterine CS.

Is postoperative computed tomography evaluation a prognostic indicator in patients with optimally debulked advanced ovarian cancer?

OBJECTIVE: To compare the surgeon's intraoperative assessment of residual tumor (RT) disease with that identified on postoperative computed tomography (CT) in patients undergoing optimal primary surgical cytoreduction (RT <1 cm) and to identify the prognostic significance of postoperative CT scan of RT. METHODS: Patients with FIGO stage III-IV ovarian cancer treated at the Gynecologic Oncology Unit of the National Cancer Institute between November 2011 and March 2013, who underwent optimal primary cytoreduction and were entered in prospective controlled clinical trials requiring a baseline postoperative CT evaluation within 30 days, were enrolled. All CT scans were reviewed by a dedicated radiologist to evaluate RT. Median follow-up was 16 months. RESULTS: 64 out of 160 patients met the eligibility criteria. RT = 0, 0.1 < RT < 0.5 cm, and 0.6 < RT < 1 cm was reported in 53 (82.8%), 9 (14.1%) and 2 (3.1%) cases, respectively. Postoperative CT disagreed with RT in 13 out of 64 (20.3%) cases. Progression-free survival (PFS) of patients with a positive and negative postoperative CT scan of RT was 5 months (95% CI 1-15 months) and 28 months (95% CI 2-46 months), respectively (p < 0.0001). Evidence of the disease using postoperative CT was an independent prognostic factor in multivariate analysis (HR = 8.87, 95% CI = 3.23-24.31, p < 0.0001). CONCLUSIONS: Evidence of the disease using postoperative CT was associated with a significant decrease in PFS in patients who underwent optimal primary cytoreduction. RT status as evaluated with early postoperative CT may have an important role in prognostic assessment.