Manuela Monti

Treatment with the radiolabelled somatostatin analog Lu-DOTATATE for advanced pancreatic neuroendocrine tumors

Background: We evaluated the activity and safety profile of 177Lu-DOTATATE peptide receptor radionuclide therapy (Lu-PRRT) in patients with advanced G1-G2 pancreatic neuroendocrine tumors. Patients and Methods: Fifty-two consecutive patients were treated at two different therapeutic dosages of 18.5 or 27.8 GBq in five cycles, according to the patients kidney function and bone marrow reserve, which are known to be the critical organs in PRRT. Results: Twenty-six patients received a mean full dosage (FD) of 25.5 GBq (range 20.7-27.8) and 26 a mean reduced dosage (RD) of 17.8 GBq (range 11.1-19.9). Both therapeutic dosages resulted in antitumor activity (disease control rate in the entire case series 81%), with 12% complete response, 27% partial response and 46% stable disease in the FD group, whereas we observed 4% complete response, 15% partial response and 58% stable disease in the RD group. Median progression-free survival was not reached in the FD group and was 20 months in the RD group. No major acute or delayed hematological toxicity occurred. Conclusion:177Lu-DOTATATE peptide receptor radionuclide therapy showed antitumor activity in advanced pancreatic neuroendocrine tumors even at a reduced total activity of 18.5 GBq. However, progression-free survival was significantly longer (p = 0.05) after a total activity of 27.8 GBq, which can thus be considered the recommended dosage in eligible patients.

Metronomic capecitabine in gastroenteropancreatic neuroendrocrine tumors: a suitable regimen and review of the literature.

Background We present a retrospective analysis of metronomic capecitabine in metastatic gastroenteropancreatic neuroendrocrine tumors (GEP-NETs). A review of the literature is also presented. Methods From January 2007 to December 2013, ten patients with metastatic GEP-NETs (four pancreatic and six ileal) who progressed after treatment with somatostatin analogs and other cytotoxic agents received oral capecitabine 1,500 mg/day continuously. The median patient age was 68 (range 29–82) years. The median treatment duration was 8 months. Results Five (50%) patients achieved a partial radiographic response, four (40%) showed stable disease, and one (10%) progressed. Median overall survival was 56 months. Three of the four pancreatic patients achieved a partial radiographic response that lasted for a median of 15.5 months; overall survival and progression-free survival in this subgroup was 58 and 6 months, respectively. Conclusion Data in the literature show that capecitabine has only occasionally been used as a single agent, with increased toxicity. Only one study using single-agent capecitabine reported a progression-free survival of 9.9 months and overall survival of 36.5 months, without an objective response or major toxicity. In our experience, metronomic capecitabine was well tolerated, although minor side effects may have been underestimated due to the retrospective nature of our study. This regimen also seems to be feasible in elderly people. Although high response rates and prolonged response duration indicate the potential efficacy of this treatment, our results should be interpreted cautiously because of the small number of patients involved. Capecitabine was most effective in the pancreatic subgroup, which would seem to be more sensitive to chemotherapy.

Docetaxel followed by gemcitabine in the treatment of advanced non-small cell lung cancer: a phase I study.

Aims and Background Based on the results of a preclinical study, a phase I trial was conducted to evaluate the feasibility of administering docetaxel followed by gemcitabine in non-small cell lung cancer patients. Study design Sixteen patients with advanced non-small cell lung cancer (stages III B-IV) were treated on the 1st day with docetaxel and on the 8th day with gemcitabine. Treatment was repeated every three weeks for a maximum of six cycles. Five groups received docetaxel/gemcitabine (mg/m2): 50/800, 60/800, 60/900, 60/1,000, 70/1,000. All patients and 57 cycles were assessed for toxicity. Results The most important side effects were grade IV neutropenia in 4 patients (2 at the 60/1000 level and 2 at the 70/1000 level) and grade III leukopenia and neutropenia without fever in 4 and 6 patients, respectively. Maximum tolerated dose was not reached. Conclusions The sequence docetaxel → gemcitabine appears well tolerated and easy to administer. For this reason, a phase II study is ongoing to fully assess its antitumor activity.

Endobronchial/Endoesophageal Ultrasound (EBUS/EUS) Guided Fine Needle Aspiration (FNA) and 18F-FDG PET/CT Scanning in Restaging of Locally Advanced Non-small Cell Lung Cancer (NSCLC) Treated with Chemo-radiotherapy A Mono-institutional Pilot Experience

Chemo-radiotherapy is standard treatment of stage IIIA-N2 bulky or IIIB non-small cell lung cancer (NSCLC). Surgical resection of residual disease in downstaged patients may improve overall survival. In this setting, restaging disease is still a challenge. 18F-FDG PET/CT represents the gold standard although accuracy results are disappointing. Endoscopic bronchial/ esophageal ultrasound (EBUS/EUS)-guided fine needle aspiration (FNA) may confirm lymph node (LN) involvement. We analyzed 16 patients with stage IIIA-N2 bulky or IIIB NSCLC treated with chemo-radiotherapy. At restaging, all patients performed EBUS/EUS with FNA and PET/CT scan and results were compared. Patients underwent PET/CT scan 43 days (range: 24-89) and EBUS/EUS 42 days (range: 14-71) after therapy. Overall, 7 EBUS and 9 EUS procedures were performed: no complications resulting from the procedure occurred. In 6 patients EBUS/EUS did not reveal any suspicious lesions; in 2 the exam showed enlarged mediastinal LN that were biopsied, but with no evidence of tumor cells; in 2 the sample was not considered diagnostic; 6 had persistent mediastinal LN involvement. PET/CT scan showed 4 cases of complete metabolic response, 9 partial metabolic response, 2 stable metabolic disease and one progressive metabolic disease. Notably, all 7 patients with .80% decrease in SUV with respect to basal value showed a pathological complete response or negative EBUS/EUS. EBUS/EUS could be used to complement PET/CT scanning to verify mediastinal LN clearance. Further prospective trials are warranted to confirm the utility of EBUS/EUS together with PET/CT in restaging locally advanced NSCLC.

New requirements for phase I trials: a challenge for Italian clinical research.

Background: In 2015, the Italian Medicines Agency (Agenzia Italiana del Farmaco; AIFA) issued the Determination 809/2015 with new requirements for phase I clinical trials. Before it came into force, we explored the extent to which several Italian oncology centers were working to implement it. Methods: A survey was conducted among 80 Italian centers involved in clinical trials. Investigators and research coordinators were surveyed. Results: Answers from 42 institutions were collected: among them 88.1% were involved in oncology research. In the last 5 years, 55% had conducted from 1 to 5 phase I trials, and only 16.7% more than 5. A third were involved in not-first-in-human research and none with healthy volunteers. The majority (57.1%) of the centers did not run any projects and trials are non-commercial, and about 35%, no more than 2. While 9.5% already met the standards for self-certification, 71.4% were working to achieve them. Standard operating procedures dedicated to research and the required good clinical practice training had been established by 57.1% and 76.2%, respectively. Fifty percent of laboratories were almost compliant with the Determination. After 10 months from its coming into force, 98 sites had applied for certification, of which 34 were oncology units. Conclusions: The new AIFA Determination imposes a certified organizational model on units and laboratories involved in phase I trials. Our results showed that great efforts were made to qualify for phase I research suggesting that other oncology units will apply for certification in the near future. Predictably, Italy will set the pace as a highly qualified country in which to conduct early-phase research.

Treatment of squamous cell carcinoma of the anal canal: A new strategies with anti-EGFR therapy and immunotherapy

The incidence of squamous cell carcinoma of the anal canal (SCAC) is increasing in both sexes but the standard treatment remains that of 20 years ago. However, interesting data have recently emerged on the use of anti-epidermal growth factor receptor (EGFR) agents and immunotherapy in advanced disease. Thus, new avenues of research are opening up that will hopefully lead to more effective therapeutic strategies. We provide an overview of the latest studies published on this tumor and discuss the possible future therapeutic options for combination therapy, anti-EGFR treatment and radiotherapy.

Terapia radiorecettoriale dei tumori neuroendocrini pancreatici

SommarioLa terapia radiorecettoriale con 177Lu-DOTATATE (Lu-PRRT) è una valida opzione di terapia mirata nei tumori neuroendocrini pancreatici G1–G2 (pNET). È una terapia efficace in oltre l’80% dei casi. Complessivamente è ben tollerata, con tossicità midollare e renale lieve e reversibile, in particolare con frazionamento della dose totale di radiofarmaco. Nella gestione dei pazienti pNET, la PET con FDG è un importante fattore prognostico legato al metabolismo glucidico tumorale.

111In-Pentetreotide (OctreoScan) scintigraphy in the staging of small-cell lung cancer: Its accuracy and prognostic significance

Background Small-cell lung cancer (SCLC) may express somatostatin transmembrane receptors (SSTRs) in 50–75% of cases. We evaluated the accuracy and prognostic significance of somatostatin receptor scintigraphy (SSRS) in staging compared with conventional radiological procedures. Patients and methods Newly diagnosed SCLC patients underwent scintigraphy with the radiolabeled somatostatin analog indium-111 (111In)-pentetreotide (OctreoScan). Histological data were available for 20 (38%) patients for immunohistochemical analysis of SSTR-2 expression. Results From May 2007 to December 2011 we analyzed 52 SCLC patients. In comparison with standard radiologic staging, the sensitivity and specificity of SSRS were 63 and 100% for primary pulmonary tumor (T), 51 and 100% for mediastinal lymph node (N), and 23 and 91% for metastatic disease (M), respectively. The overall SSRS accuracy was 65% for T, 62% for N, and 52% for M. Patients with positive SSRS achieved a disease control rate of 97 versus 84% in those with negative exam results; median progression-free survival was 9.5 months versus 11.0 and median overall survival was 15.3 versus 14.5 months for patients with positive SSRS versus those with a negative result. Notably, seven (78%) patients with a positive quantitative analysis for SSTR-2 had a positive SSRS; at semiquantitative analysis this correlation was found in eight (73%) patients. Conclusion SSRS has a lower accuracy in comparison with standard radiological staging in SCLC. However, patients with a positive SSRS given standard treatments showed better disease control compared with those with a negative SSRS, but similar progression-free survival and overall survival.

Contents Vol. 97

D.H. Abbott, Madison, Wisc. E. Arzt, Buenos Aires A.V. Babwah, London, Ont. T. Bartness, Atlanta, Ga. C.L. Bethea, Beaverton, Oreg. D.W. Brann, Augusta, Ga. B. Canny, Monash, Vic. M. Caplin, London K. Catt, Bethesda, Md. A. Chodobski, Providence, R.I. S.L. Dickson, Gothenburg J. Drouin, Montreal, Que. P.J. Enriori, Monash, Vic. W. Farrell, Keele M. Freeman, Tallahasse, Fla. A.C. Gore, Austin, Tex. K. Grove, Beaverton, Oreg. T. Harmar, Edinburgh A. Herbison, Dunedin J. Herman, Cincinnati, Ohio J.J. Hirst, Callaghan, N.S.W. T. Hökfelt, Stockholm U. Kaiser, Boston, Mass. K. Kim, Seoul J.Z. Kiss, Geneva A.C. Latronico, São Paulo G. Leng, Edinburgh J. Levine, Evanston, Ill. C. Libertun, Buenos Aires C. Llorens-Cortes, Paris A. Lomniczi, Beaverton, Oreg. A. Loudon, Manchester Z.-L. Lu, Edinburgh G. Martinez de la Escalera, Querétaro R. Melcangi, Milano I. Modlin, New Haven, Conn. Z. Naor, Tel Aviv M. Palkovits, Budapest I. Parhar, Kuala Lumpur D.W. Pfaff, New York, N.Y. T.M. Plant, Pittsburgh, Pa. J. Reul, Bristol R. Reynolds, Edinburgh E. Rissman, Charlottesville, Va. J.L. Roberts, San Antonio, Tex. I. Robinson, London P. Ruszniewski, Clichy W. Schlegel, Geneva D. Skinner, Laramie, Wyo. M. Sleeman, Clayton, Vic. J. Smith, Perth, W.A. E. Spinedi, La Plata R. Steiner, Seattle, Wash. E. Terasawa, Madison, Wisc. A. Tilbrook, Roseworthy, S.A. E. Wagner, Pomona, Calif. B. Walker, Edinburgh H. Watanobe, Chiba M. Watt, Clayton, Vic. M. Wierman, Denver, Colo. J. Wingfield, Seattle, Wash. S. Wray, Bethesda, Md. International Journal for Basic and Clinical Studies on Neuroendocrine Relationships

Erratum: Multicenter Institutional Experience of Surgically Resected Thymic Epithelial Tumors (TETs): An Observational Report on Behalf of F.O.N.I.C.A.P. (Forza Operativa Nazionale Interdisciplinare Contro il Cancro del Polmone) (Ann Surg Oncol DOI: 10.1245/S10434-013-3018-2)

Department of Clinical Oncology, Cervesi Hospital, Cattolica, RN, Italy; Department of Thoracic Surgery, University Hospital, Parma, Italy; Department of Medical Oncology, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST-IRCCS), Meldola, Italy; Department of Thoracic Surgery, Morgagni-Pierantoni Hospital, Forlı̀, Italy; Unit of Biostatistics and Clinical Trials, IRST-IRCCS, Meldola, Italy; Department of Medical Oncology, University Hospital, Verona, Italy; Department of Thoracic Surgery, S. Carlo Borromeo Hospital, Milan, Italy; Department of Medical Oncology, Santa Maria delle Croci Hospital, Ravenna, Italy; Department of Clinical Oncology, Maggiore della Carità Hospital, Novara, Italy; Radiology Unit, IRST-IRCCS, Meldola, Italy