Neuroendocrine tumour arising inside a retro-rectal tailgut cyst: report of two cases and a review of the literature

Tailgut cysts (or retro-rectal cyst-hamartomas (RCHs)) are developmental abnormalities consisting of multiloculated cysts lined by squamous, transitional or glandular epithelium which, albeit rarely, may give rise to malignant transformations. Carcinoid tumours arising in the presacral region are extremely rare and usually benign, and only a few are described in the literature. Case 1: A 63-year-old female diagnosed as having bilateral ovarian cysts underwent surgery to remove a right adnexial mass that was histopathologically diagnosed as a well-differentiated carcinoid tumour. She is currently disease free after 18 months of follow-up. Case 2: A 41-year-old-female diagnosed with hepatic metastases and a solid pelvic mass arising from a moderately differentiated neuroendocrine carcinoma is currently alive with disease after having undergone surgical removal of the mass and several medical treatments. We here describe two different clinical histories of well- and moderately differentiated neuroendocrine tumours (NETs) arising from tailgut cysts in the prerectal space together with a review of the relevant literature

Three-times daily radiotherapy after chemotherapy in stage III non-small cell lung cancer. Single-institution prospective study

Aim: A prospective study for stage IIIA-B non-small cell lung cancer (NSCLC), with three-times daily (3td) radiotherapy (RT), after induction chemotherapy (iCT), with or without surgery. Patients and Methods: Induction cisplatin and gemcitabine chemotherapy was delivered. Surgery and postoperative (post-op) radiotherapy were planned for responsive stage IIIA patients; definitive irradiation was performed in unresectable III A and IIIB patients. Doses of 54.4 and 64.6 Gy were delivered for the post-op and definitive treatments, respectively. Results: Out of 52 patients (pts), 37 received 3tdRT as definitive (18 pts) or post-op treatment (19 pts). Overall, the failures were similar between post-op and definitive 3tdRT (78.9% vs. 77.8%). In the post-op treatment, metastases and local failures were 52.6% and 10.5%, respectively and in the definitive radiotherapy, the incidence was similar (local 33.3% vs. systemic 44.4%). The five-year overall survival (OS) was 25% for the post-op and 21% for the definitive patients (p=0.87). Conclusion: Three-times daily postoperative radiotherapy did not improve the outcome in NSCLC, but for unresectable patients, this approach may have a role in selected cases

Neoadjuvant eribulin mesylate following anthracycline and taxane in triple negative breast cancer: Results from the HOPE study

Background Eribulin mesylate (E) is indicated for metastatic breast cancer patients previously treated with anthracycline and taxane. We argued that E could also benefit patients eligible for neoadjuvant chemotherapy. Methods Patients with primary triple negative breast cancer 2 cm received doxorubicin 60 mg/m2 and paclitaxel 200 mg/m2 x 4 cycles (AT) followed by E 1.4 mg/m2 x 4 cycles. Primary endpoint was pathological complete response (pCR) rate; secondary and explorative endpoints included clinical/metabolic response rates and safety, and biomarker analysis, respectively. Using a two-stage Simon design, 43 patients were to be included provided that 4 of 13 patients had achieved pCR in the first stage of the study. Results In stage I of the study 13 women were enrolled, median age 43 years, tumor size 2–5 cm in 9/13 (69%), positive nodal status in 8/13 (61%). Main grade 3 adverse event was neutropenia (related to AT and E in 4 and 2 cases, respectively). AT followed by E induced clinical complete + partial responses in 11/13 patients (85%), pCR in 3/13 (23%). Median measurements of maximum standardized uptake value (SUVmax) resulted 13, 3, and 1.9 at baseline, after AT and E, respectively. Complete metabolic response (CMR) occurred after AT and after E in 2 and 3 cases, respectively. Notably, 2 of the 5 (40%) patients with CMR achieved pCR at surgery. Immunostaining of paired pre-/post-treatment tumor specimens showed a reduction of β-catenin, CyclinD1, Zeb-1, and c-myc expression, in the absence of N-cadherin modulation. The study was interrupted at stage I due to the lack of the required patients with pCR. Conclusions Despite the early study closure, preoperative E following AT showed clinical and biological activity in triple negative breast cancer patients. Furthermore, the modulation of β-catenin pathway core proteins, supposedly outside the domain of epithelial–mesenchymal transition, claims for further investigation. Trial registration EU Clinical Trial Register, EudraCT number 2012-004956-12

QTc prolongation assessment in anticancer drug development: clinical and methodological issues

Cardiac safety assessments are commonly employed in the clinical development of investigational oncology medications. In anti-cancer drug development there has been increasing consideration for the potential of a compound to cause adverse electrocardiographic changes, especially QT interval prolongation, which can be associated with risk of torsades de pointes and sudden death. Irrespective of overt clinical toxicities, QTc assessment can potentially influence decision making at many levels during the conduct of clinical studies, including eligibility for protocol therapy, dose delivery or discontinuation, and analyses of optimal dose for subsequent development. Given the potential for serious and irreversible morbidity from cardiac adverse events, it is understandable that cardiac safety results can have broad impact on study conduct and patient management. The methodologies for risk management of QTc prolongation for non cardiac drugs have been developed out of experiences primarily from drugs used to treat non life-threatening illnesses in a chronic setting such as antibiotics or antihistamines. Extrapolating these approaches to drugs for treating cancer over an acute period may not be appropriate. Few specific guidelines are available for risk management of cardiac safety in the development and use of oncology drugs. In this manuscript, clinical and methodological issues related to QTc prolongation assessment will be reviewed. Discussions about limitations in phase-I design and oncology drug development will be highlighted. Efforts are needed to refine strategies for risk management, avoiding unintended consequences that negatively affect patient access and clinical development of promising new cancer treatments. A thoughtful risk management plan generated by an organized collaboration between oncologists, cardiologists, and regulatory agencies to support a development programme essential for oncology agents with cardiac safety concerns

Gemcitabine-induced systemic capillary leak syndrome

Systemic capillary leak syndrome (SCLS) is a rare disorder with a high mortality rate, characterized by rapidly developing edema, weight gain and hypotension, hemoconcentration and hypoproteinemia. This syndrome is caused by sudden, reversible capillary hyperpermeability with a rapid extravasation of plasma from the intravascular to the interstitial space. Even though SCLS has been suggested to be the pathogenic mechanism for the pulmonary toxicity of gemcitabine (GCB), a new deoxycytidine analogue with structural similarities to cytosine arabinoside, a direct correlation between GCB and SCLS has never been reported. We describe a case of repeated SCLS after GCB administration in a 51-year-old male with locally-advanced non-small-cell lung cancer treated with a combination of cisplatin and GCB. The detection of GCB-induced SCLS supports the hypothesis that SCLS could be the pathogenic way of GCB pulmonary toxicity. This finding can help to better understand and treat the potentially deadly GCB-related acute respiratory distress syndrome that is being recognize

Imatinib administration in two patients with liver metastases from GIST and severe jaundice

Imatinib is the only effective and approved systemic therapy for the treatment of patients with advanced gastrointestinal stromal tumours (GISTs). Although metastases from GISTs most commonly involve the liver, yielding hyperbilirubinaemia, very few data on imatinib administration in subjects with jaundice are available. We provide evidence that imatinib tolerability was not adversely affected by jaundice in two patients with advanced GIST

Efficacy and safety of immunotherapy in elderly patients with non-small cell lung cancer

OBJECTIVES: Most trials with Immune Checkpoint Inhibitors (ICIs) for Non-Small Cell Lung Cancer (NSCLC) included only small subgroups of patients aged 6565. As NSCLC is often diagnosed in patients aged 6570, real-world data about efficacy and safety of immunotherapy (IO) in elderly patients are essential. MATERIALS AND METHODS: We retrospectively collected data about all patients with advanced NSCLC treated with IO at our Institution between April 2013 and March 2019. The patients were stratified for age as follows: <70 year-old, 70-79 year-old, 6580 year-old. Chi-square test was used to compare qualitative variables. Survival was estimated with Kaplan-Meier method. Log-rank test was used to compare curves. Multivariate analyses were performed with Cox model. RESULTS: We reviewed 290 cases, with a median age of 67 (range: 29-89). Patients aged<70, 70-79 and 6580 year-old were 180, 94 and 16, respectively. Clinical/pathological variables were uniformly distributed across age classes, except for a higher rate of males (p 0.0228) and squamous histology (p 0.0071) in the intermediate class. Response Rate (RR) was similar across age groups (p 0.9470). Median Progression Free Survival (PFS) and Overall Survival (OS) did not differ according to age (p 0.2020 and 0.9144, respectively). Toxicity was comparable across subgroups (p 0.6493). The only variables influencing outcome were performance status (PS) (p\u2009<\u20090.0001 for PFS, p 0.0192 for OS), number of metastatic sites (p 0.0842 for PFS, p 0.0235 for OS) and IO line (p\u2009<\u20090.0001 for both PFS and OS). CONCLUSION: Advanced age was not associated to a reduced efficacy of IO in our case series. Furthermore, no toxicity concern emerged even among the eldest pts. To our opinion, ICIs should be considered irrespective of age, provided an optimal PS at baseline. Of note, IO is often the only therapeutic option applicable to these cases considering the toxicity of chemotherapy