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Background: Treatment for locally advanced differentiated thyroid cancer is surgery followed by radioiodine while the role of adjuvant external beam radiotherapy (EBRT) is debated., Methods: The panel of the Italian Association of Radiotherapy and Clinical Oncology developed a clinical recommendation on the addition of EBRT to radioiodine after surgery for locally advanced differentiated thyroid cancer by using the Grades of Recommendation, Assessment, Development, and Evaluation methodology and the Evidence to Decision framework. A systematic review with meta-analysis about this topic was conducted with a focus on outcome of benefits and toxicity., Results: Locoregional control was improved by EBRT while no considerable toxicity impact was reported., Conclusion: The panel judged uncertain the benefit/harms balance; final recommendation was conditional both for EBRT + radioiodine and radioiodine alone in the adjuvant setting.

Currently, conventional treatments for metastatic RCC (mRCC) include immune-based combination regimens and/or targeted therapies, the latter mainly acting on angiogenesis, a key element of the process of tumor growth and spread. Although these agents proved able to improve patients' outcomes, drug resistance and disease progression are still experienced by a substantial number of VEGFR-TKIs-treated mRCC patients. Following the inhibition of the VEGF/VEGFRs axis, two strategies have emerged: either specifically targeting resistance pathways, at the same time continuing to inhibit angiogenesis, or using a completely different approach aimed at re-activating the immune system through the use of inhibitors of specific negative immune checkpoints. These two approaches, practically represented by the use of either cabozantinib or nivolumab, seem to remain a rational therapeutic approach also when first-line immune-based combinations are used. The objective of this study is to design a preferential therapeutic pathway for the second-line treatment of mRCC. The procedure applied in this project was a group discussion, based on the Nominal Group Technique (NGT) method in a meeting session, aimed at defining the therapeutic choice for the second-line treatment of mRCC. The NGT process defined the most relevant parameters that, according to the interviewed panelists, clinicians should consider for the selection of the second-line therapy in the context of advanced renal cell carcinoma of mRCC. The algorithm developed for the treatment selection as a result of this process should thus be considered by clinicians as reference for therapy selection., Plain Language Summary: The result of this paper was the definition of an algorithm intended to suggest a preferential therapeutic pathway considering both the outputs of the Nominal Group Technique (NGT) process and the actual clinical practice and the experience of selected panelists. During the NGT process and the discussion phase, panelists defined the most important parameters to be included in the algorithm that are important for the treatment definition. Cabozantinib and nivolumab are identified as the most reasonable therapeutic options for patients progressing after first-line treatment and are the medication options included in the algorithm for therapy selection., Competing Interests: Conflict of interest statement: - Valentina Guadalupi in the last two years has had financial or working relationships with Janssen - Giacomo Cartenì works as responsible for research and development at Kerubin Digital Therapeutic - Roberto Iacovelli acted as a Consultant and/or a Speaker for Pfizer, Ipsen, MSD, Sanofi, Janssen - Camillo Porta acted as a Consultant and/or a Speaker for Ipsen, BMS, MSD, Astra Zeneca, Pfizer, Eisai, EUSA and General Electrics; he acted also as an Expert Testimony for both Pfizer and EUSA and is a protocol steering committee member for BMS, EUSA and Eisai - Giovanni Pappagallo acted as a Consultant and/or Speaker (training or advisory board or clinical epidemiological evaluations) for Astellas, AstraZeneca, Clovis, Ipsen, Janssen, MSD. Pierre Fabre, Pfizer, Roche, Sanofi, Servier, Teva - Riccardo Ricotta acted as a Consultant and/or a Speaker for BMS, Ipsen, Janssen, MSD, Pfizer, Sanofi-Genzyme - Giuseppe Procopio acted as a Consultant and/or a Speaker for Bayer, BMS, Novartis, Amgen, Pfizer, Janssen, Ipsen, Boehringer, (© The Author(s), 2021.)

Randomized clinical trials are the gold standard to test the efficacy of an intervention within a specified patient population. However, the results of the trials may not be generalizable to routine clinical practice. Observational cohort studies may provide information that complements trial results. Targeted therapies are characterized by tolerability profiles that may differ from those of 'traditional' chemotherapy. Therefore, the post-approval evaluation of these drugs by large, well-designed observational cohort studies in real life populations is warranted. Everolimus is an orally-administered inhibitor of the mammalian target of rapamycin. A number of observational cohort studies have been conducted to characterize the effectiveness and safety of everolimus in clinical practice. In particular, the ORCHIDEE study was designed to identify factors predictive of favorable outcome in patients treated with everolimus such as second-line treatment for metastatic renal cell carcinoma after failure of a first-line treatment with a VEGF TKI. ORCHIDEE is a multicenter, single-arm, phase IV study. The study will enroll approximately 200 metastatic renal cell carcinoma metastatic renal cell carcinoma patients from 20 Italian centers over a 24-month period.

Thirty-four evaluable patients with metastatic colorectal carcinoma (13 rectal primary and 21 colonic primary, 4 pretreated and 30 untreated) received 4'epi-doxorubicin at the dose of 75 mg/m2 i.v. once every 21 days, for a minimum of 2 courses. Symptomatic toxicity (mainly confined to gastrointestinal complaints) was short-lived and easily managed. Hematologic toxicity was mild. Transient electrocardiographic abnormalities were found in 50% of patients, without signs of significant cumulative cardiotoxicity. Three previously untreated patients achieved a partial response (lasting 16, 12 and 12 weeks, respectively) with a response rate of 9% (3%-23%, 95% confidence interval). More interestingly, all responsive patients had rectal cancer: further studies of 4'epi-doxorubicin confined to the rectal localization seem warranted.

Eighteen evaluable patients with advanced malignant lymphoma were treated with a combination of cis-dichlorodiammineplatinum (II) (50 mg/m2 i.v. on day 1), VP 16-213 (100 mg/m2 i.v. on days 1, 3, 5), and prednisone (50 mg/m2 per os on days 1-5), recycling every 2 weeks. All patients were previously pretreated. There were 3 complete remissions (patients with Hodgkin's disease), and 4 partial remission (2 patients with Hodgkin's and 2 with non-Hodgkin's lymphoma), for a median duration of 8 weeks. In addition, 2 minor responses (patients with Hodgkin's disease) were observed. Vomiting and myelosuppression were the most prominent toxic effects. In most heavily pretreated patients, myelosuppression was moderate to severe: in these patients and in patients with bone marrow involvement, a schedule interval of 3 weeks should be more appropriate. Nephrotoxicity was minimal. This combination chemotherapy showed some activity in the management of advanced malignant lymphomas; further studies in this area are justified.

The antineoplastic activity of vindesine was evaluated in 57 patients with non-small-cell carcinoma of the lung, 53 patients were fully evaluable for response and toxicity. Twenty-seven patients had squamous cell carcinoma (WHO I), 14 had adenocarcinoma (WHO III), and 12 had large cell carcinoma (WHO IV). Forty percent of patients were previously treated. Vindesine was administered at a weekly i.v. dose of 3 mg/m2. Partial remissions were observed in 2 of 12 patients with large cell carcinoma and in 1 of 27 patients with squamous cell carcinoma. Among 14 patients with adenocarcinoma, 3 minor responses were observed. Drug-related toxic effects (mainly leukopenia with manageable and reversible neurotoxicity) required modification of dose in 41% of patients: this finding and previous treatment may have adversely affected the response rate. It is concluded that vindesine as a single agent has some activity in large cell carcinoma. Activity in the other histologic types was minimal but not totally absent and deserves further evaluation, possibly in non-pretreated patients.

Serum copper level (SCL) was studied by the atomic absorption technique in 103 patients with non-Hodgkin's lymphoma. SCL was increased in 61% of patients at diagnosis or during active disease; values within normal range were found in 88% of patients in complete remission. The difference between mean SCL during active disease and in remission was highly significant, independently of stage and histologic type, so that: a) Within the same clinical stage high SCL at diagnosis was associated with poorer response to therapy in stage II and stage III (respectively P = 0.033 and P = 0.049), but not in stage IV, where the complete remissions were only 8 out of 42. A shorter 5-year survival was also shown in stages III and IV with high SCL at diagnosis (respectively P less than 0.025 and P less than 0.05), but not in stage II where the deaths were only 3 out of 24. b) Within histologic types, SCL is a useful prognostic index of response to therapy and survival, although a statistically significant difference was only reached for poorly differentiated lymphocytic lymphoma. We conclude that SCL may be a good parameter of disease activity and a useful index of response to therapy and survival in non-Hodgkin's lymphoma.

From March 1981 to January 1984, 116 patients with advanced non-small-cell carcinoma of the lung (NSCCL) were randomly assigned to 3 combinations as follows: CDDP + DVA, CDDP + VP16 and DXR + CTX. 94 patients were evaluable for response, 106 for toxicity and survival. Of 31 patients, 15 (48%; 3 CRs and 12 PRs) responded to CDDP + DVA; of 33 patients, 12 (36%, 2 CRs and 10 PRs) responded to CDDP + VP16; of 30 patients, 3 (10%) obtained a PR with DXR + CTX (CDDP + DVA vs DXR + CTX, P less than 0.005; CDDP + VP16 vs DXR + CTX, P less than 0.05; CDDP + DVA vs CDDP + VP16, P = NS). The median duration of response was 22 weeks in the CDDP-DVA group, 17 weeks in the CDDP-VP16 group, and 16 weeks in the DXR + CTX group. No significant difference in survival was observed among the 3 groups (median: 43, 47, 41 weeks, respectively). Hematologic and neurologic toxicities were significantly higher in the DVA-containing regimen. Despite the lack of improvement of overall survival with the CDDP-containing combinations over the DXR + CTX control group, the good response rate makes them suitable to be used in combined therapeutic strategies.

We conducted a phase II trial of Vindesine in 24 patients, mostly pretreated (23/24 fully evaluable for therapeutic response) with advanced hematologic malignancies. The drug was administered at weekly bolus doses of 3 mg/m2 i.v. Overall, objective tumor regressions were seen in 9 of 23 patients. The drug appeared effective in extraosseous plasmacytoma (1 complete response, 1 partial response and 1 minor response in 6 patients). Further phase II trials in these 2 diseases are justified. In addition, 3 partial responses in 7 patients with advanced lymphoma were also obtained. Previous vinca-alkaloid exposure did not adversely affect the response rate: 8 of 9 responsive patients had previously received vincristine and/or vinblastine. Drug-related toxic effects were mainly represented by manageable and reversible neurotoxicity and by moderate leukopenia with apparent lack of thrombocytopenia. In heavily pretreated patients, leukopenia may be occasionally severe: in these conditions a starting dose of 2 mg/m2 seems more appropriate.