Recurrent gastric amphicrine tumor with neuroendocrine and pancreatic acinar cell differentiation and somatic MEN1 inactivation arisen during immunotherapy.

Amphicrine neoplasms (ANs) are poorly understood epithelial malignancies composed of cells with co-existing exocrine-neuroendocrine features. Here, we report a recurrent mucin-producing gastric amphicrine tumor co-expressing neuroendocrine (chromogranin-A, synaptophysin, and CD56) and pancreatic acinar cell (BCL10 and trypsin) markers, arisen in a 64-year-old woman during adjuvant immunotherapy for melanoma. Ki-67 was < 2%. The gastric background context was atrophic gastritis. Next-generation sequencing showed MEN1 mutation (p.P71fs*42) coupled with loss of heterozygosity. The key lessons were as follows: (1) gastric ANs can show the co-existence of exocrine mucin-producing elements with neuroendocrine and pancreatic acinar differentiation; (2) they may represent a new entity arising in the context of atrophic gastritis and during immunotherapy; (3) they should be considered in the diagnostic workup of gastric neuroendocrine tumors; and (4) their molecular profile can show striking similarities with well-differentiated neuroendocrine tumors. These findings may be of help to improve the knowledge and the biological taxonomy of ANs.

Real world data of cemiplimab in locally advanced and metastatic cutaneous squamous cell carcinoma.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) has an overall favourable outcome, except for patients with an advanced stage disease. The programmed death protein-1 (PD-1) inhibitor cemiplimab has been approved for use in advanced cSCC. We report clinical outcomes from the named patient programme-compassionate use of cemiplimab for patients with advanced cSCC in Italy. METHODS: This is a retrospective, observational, multicentre study. We analysed medical records of patients with advanced cSCC treated with cemiplimab between May 2019 and February 2020 in 17 referral Italian centres. We assessed the safety profile according to the Common Terminology Criteria for Adverse Events, version 5.0 (CTCAE v 5.0), the clinical activity in terms of response rate, clinical benefit and duration of response and baseline clinical-pathologic characteristics associated with response. RESULTS: 131 patients were included, with a median age of 79 years. Of them, 9.2% had a concurrent chronic lymphoproliferative disease and 8.5% a concomitant autoimmune disease. Some 42.7% of the total patients had at least one treatment-related adverse events (AEs); out of above, 9.2% had grade 3-4 adverse events, and there were two fatal adverse events. The overall response rate (ORR) was 58%, and the disease control rate (DCR) was 71.7%. Cutaneous squamous cell carcinomas (cSCCs) arising on the head and neck area (p = 0.007) and haemoglobin values in normal range (p = 0.034) were significantly associated with a better response, while cSCCs on the genitalia (p = 0.041), treatment with any systemic antibiotic within 1 month of cemiplimab initiation (p = 0.012), performance status ≥1 (p = 0.012), chronic corticosteroids therapy (p = 0.038), previous radiation therapy to lymph nodes (p = 0.052) and previous chemotherapy (p = 0.0020) were significantly associated with a worse response. CONCLUSIONS: Our real-world study showed safety and effectiveness results comparable to those obtained in clinical trials. We identified some clinical and biochemical factors potentially associated with response to cemiplimab.

Influence of different lipid emulsions on specific immune cell functions in head and neck cancer patients receiving supplemental parenteral nutrition: An exploratory analysis.

OBJECTIVES: The effect of diet on immune responses is an area of intense investigation. Dietary lipids have been shown to differently influence and fine-tune the reactivity of immune cell subsets, thus potentially affecting clinical outcomes. Patients with head and neck squamous cell carcinoma face malnutrition, due to swallowing impairment related to the tumor site or to treatment sequalae, and may need supplemental parenteral nutrition (SPN) in addition to oral feeding when enteral nutrition is not feasible. Additionally, immune depression is a well-known complication in these patients. Parenteral nutrition (PN) bags contain amino acids, minerals, electrolytes and mostly lipids that provide calories in a concentrated form and are enriched with essential fatty acids. The aim of this study was to investigate multiple parameters of the immune responses in a cohort of patients with head and neck squamous cell carcinoma undergoing supplemental PN with bags enriched in ω-3 or ω-9 and ω-6 fatty acids. METHODS: To our knowledge, this was the first exploratory study to investigate the effects of two different PN lipid emulsions on specific immune cells function of patients with advanced head and neck squamous carcinoma. ω-3-enriched fish-oil-based- and ω-6- and ω-9-enriched olive-oil-basedSPN was administered to two groups of patients for 1 wk in the context of an observational multicentric study. Polychromatic flow cytometry was used to investigate multiple subsets of leukocytes, with a special focus on cellular populations endowed with antitumor activity. RESULTS: Patients treated with olive-oil-based PN showed an increase in the function of the innate (natural killer cells and monocytes) and adaptive (both CD4 and CD8 cells) arms of the immune response. CONCLUSION: An increase in the function of the innate and adaptive arms of the immune response may favor antitumoral responses.

Organisational challenges, volumes of oncological activity and patients' perception during the severe acute respiratory syndrome coronavirus 2 epidemic.

BACKGROUND: On February 23rd, the 1st case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was diagnosed at the University Hospital Trust of Verona, Italy. On March 13th, the Oncology Section was converted into a 22-inpatient bed coronavirus disease (COVID) Unit, and we reshaped our organisation to face the SARS-CoV-2 epidemic, while maintaining oncological activities. METHODS: We tracked down (i) volumes of oncological activities (January 1st - March 31st, 2020 versus the same period of 2019), (ii) patients' and caregivers' perception and (iii) SARS-CoV-2 infection rate in oncology health professionals and SARS-CoV-2 infection-related hospital admissions of "active"' oncological patients. RESULTS: As compared with the same trimester in 2019, the overall reduction in total numbers of inpatient admissions, chemotherapy administrations and specialist visits in January-March 2020 was 8%, 6% and 3%, respectively; based on the weekly average of daily accesses, reduction in some of the oncological activities became statistically significant from week 11. The overall acceptance of adopted measures, as measured by targeted questionnaires administered to a sample of 241 outpatients, was high (>70%). Overall, 8 of 85 oncology health professionals tested positive for SARS-CoV-2 infection (all but one employed in the COVID Unit, no hospital admissions and no treatment required); among 471 patients admitted for SARS-CoV-2 infection, 7 had an "active"' oncological disease (2 died of infection-related complications). CONCLUSIONS: A slight, but statistically significant reduction in oncology activity was registered during the SARS-CoV-2 epidemic peak in Verona, Italy. Organisational and protective measures adopted appear to have contributed to keep infections in both oncological patients and health professionals to a minimum.

Linac-based stereotactic body radiation therapy for unresectable locally advanced pancreatic cancer: risk-adapted dose prescription and image-guided delivery.

BACKGROUND: Stereotactic body radiation therapy (SBRT) represents a new treatment option for locally advanced pancreatic cancer (LAPC). An accurate treatment planning with risk-adapted dose prescription with adherence to specific dose constraints for organs at risk (OARs) and the use of daily cone beam CT (CBCT) for image guidance could allow an effective and safe treatment delivery. Here, feasibility and efficacy of SBRT in LAPC treated in our cancer care center are reported. PATIENTS AND METHODS: 33 unresectable LAPC patients underwent SBRT. In order to respect OAR dose constraints, a risk-adapted dose prescription strategy was adopted, choosing between the following schedules: 42 Gy or 45 Gy in 6 daily fractions with a biologically effective dose (BED) > 70 Gy10 or 36 Gy/6 fractions (estimating a BED 57.6 Gy10). SBRT was delivered with volumetric modulated arc technique (VMAT) and flattening filter-free (FFF) mode. Image guidance was performed by means of CBCT before every treatment session. The patients were evaluated at the end of treatment for acute toxicity and at 3, 6, and 12 months for late toxicity and treatment response. RESULTS: At the time of analysis, the median follow-up was 18 months (range 5-34 months). Prior to SBRT, 24 out of 33 patients received induction chemotherapy. Although all patients were previously judged as unresectable, 6 out of 33 (18%) underwent surgery after SBRT; all of them received a BED > 70 Gy10. One-year LC and OS were 81% and 75%, respectively. A total of 12 patients (37%) had an extra-pancreatic progression. No cases of ≥G3 acute or late toxicity were reported. CONCLUSION: In our experience, risk-adapted dose prescription and image-guided SBRT represents an effective treatment option for LAPC patients.

Cholangiocarcinoma.

Biliary tract cancer accounts for <1% of all cancers and affects chiefly an elderly population, with predominance in men. We distinguish cholangiocarcinoma (intrahepatic, hilar and distal) and gallbladder cancer, with different pathogenesis and prognosis. The treatment is based on surgery (whenever possible), radiotherapy in selected cases, and chemotherapy. The standard cytotoxic treatment for advanced/metastatic disease is represented by the combination of gemcitabine and cisplatin, whereas fluoropyrimidines are generally administered in second line setting. At the present time, no biologic drug demonstrated a clear efficacy in this cancer, although the molecular characterisation could provide a promising basis for experimental treatments. A good supportive care and an early palliative care are warranted in most patients and should be delivered as a part of a global approach.

Efficacy of trastuzumab in unselected patients with HER2-positive metastatic breast cancer: a retrospective analysis.

AIMS AND BACKGROUND: The addition of trastuzumab to chemotherapy for HER2-positive metastatic breast cancer has significantly improved progression-free survival and overall survival, although most patients develop resistance or have a primarily resistant disease. The aim of the study was to describe the efficacy and safety of a first-line treatment in unselected metastatic HER2-positive breast cancer patients, treated according to clinical practice. METHODS: From 2000 to 2009, we conducted a retrospective multi-institutional analysis of 182 consecutive patients with HER2-positive metastatic breast cancer who underwent first-line treatment with trastuzumab. The primary end points were progression-free survival and overall survival; the secondary end points were survival after progression in patients treated with second-line chemotherapy with or without trastuzumab and safety. A total of 172 patients were analyzed. RESULTS: Median progression-free survival and overall survival were 1.2 (95% CI, 1.1-1.4) and 4.4 years (95% CI, 3.6-5.4), respectively. For 100 patients who received second-line chemotherapy, median survival after progression was significantly longer in those who also received trastuzumab: 2.8 (95% CI, 2.1-4.0) versus 1.2 years (95% CI, 0.6-1.9). CONCLUSIONS: Although based on retrospective data, the study confirms the role of trastuzumab as first-line treatment in metastatic breast cancer outside of a controlled trial. Moreover, information obtained on the use of trastuzumab beyond disease progression supports its use in this setting.

ALK/EML4 fusion gene may be found in pure squamous carcinoma of the lung.

INTRODUCTION: The report of cases of lung squamous cell cancers harboring anaplastic lymphoma kinase (ALK) gene rearrangements raises the question whether this histologic subtype should be also evaluated for such molecular predictive test. METHODS: A consecutive series of 40 lung pure squamous cell carcinomas were analyzed for ALK gene status by fluorescence in situ hybridization. Squamous differentiation was validated using an immunohistochemical panel including n-p63 (p40), cytokeratin (CK) 5/6, sex-determining region Y (SRY)-Box2 (SOX2), thyroid transcription factor 1, CK7, and Napsin-A. RESULTS: Squamous differentiation was confirmed in all tumors as they stained positive for n-p63 and CK5/6 and negative for thyroid transcription factor 1 and Napsin-A. One of 40 cases (2.5%) showed an ALK rearrangement on fluorescence in situ hybridization analysis. CONCLUSIONS: ALK translocation may be found in lung pure squamous cell carcinomas. Our data suggest the opportunity to test ALK rearrangements on biopsy samples harboring squamous cell cancer differentiation.

Male breast cancer: clinical features and multimodal treatment in a retrospective survey analysis at Italian centers.

AIMS AND BACKGROUND: We report a collection of data about early breast cancer in male patients from 13 Italian institutions. METHODS AND STUDY DESIGN: We obtained data from patient charts and performed statistical analysis. The primary end points were overall survival and disease-free survival. RESULTS: A total of 205 men with invasive breast cancer was identified, with a median age of 66 years. Pathological characteristics were heterogeneous for T stage, N stage and HER2 status. Histological subtype was predominantly ductal infiltrating carcinoma. Most of them were hormone receptor positive. Mastectomy was the most common strategy. Postsurgical treatment was not standardized. Patients with large tumors were more likely to be treated with chemotherapy. Disease recurrence was associated with an ER+ and PR+ status. CONCLUSIONS: We identified a correlation between relapse and hormone receptor expression, as is the case in female breast cancer.

Single agent panitumumab in KRAS wild-type metastatic colorectal cancer patients following cetuximab-based regimens: Clinical outcome and biomarkers of efficacy.

BACKGROUND: Few data are available outlining outcomes of panitumumab in advanced colorectal cancer patients benefiting from prior cetuximab-based regimens. PATIENTS AND METHODS: Thirty patients with KRAS wild type metastatic colorectal cancer with clinical benefit from prior cetuximab-based regimens between May 2004 and October 2011 were reviewed at nine Italian Institutions. Inclusion key criteria included interruption of cetuximab for reasons other than progressive disease. Patients were classified according to prior regimens (0 or ≥1), prior response or stabilization, surgery of metastases, and Köhne prognostic score. At the time of subsequent progression, patients were treated with single agent panitumumab until progressive disease, unacceptable toxicity, or consent withdrawal. RESULTS: Panitumumab obtained 67% disease control rate and 30% objective response rate, with median PFS of 4.2 and median OS of 9.6 mo. Patients with BRAF/NRAS/PI3KCA and KRAS (by mutant enriched technique) wild-type tumors had the best chance of response to panitumumab. CONCLUSIONS: Single agent panitumumab provided significant clinical benefit in heavily pretreated patients without acquired resistance to prior cetuximab-based regimens.

True 3q chromosomal amplification in squamous cell lung carcinoma by FISH and aCGH molecular analysis: impact on targeted drugs.

Squamous lung carcinoma lacks specific "ad hoc" therapies. Amplification of chromosome 3q is the most common genomic aberration and this region harbours genes having role as novel targets for therapeutics. There is no standard definition on how to score and report 3q amplification. False versus true 3q chromosomal amplification in squamous cell lung carcinoma may have tremendous impact on trials involving drugs which target DNA zones mapping on 3q. Forty squamous lung carcinomas were analyzed by FISH to assess chromosome 3q amplification. aCGH was performed as gold-standard to avoid false positive amplifications. Three clustered patterns of fluorescent signals were observed. Eight cases out of 40 (20%) showed ≥8 3q signals. Twenty out of 40 (50%) showed from 3 to 7 signals. The remaining showed two fluorescent signals (30%). When corrected by whole chromosome 3 signals, only cases with ≥8 signals maintained a LSI 3q/CEP3 ratio >2. Only the cases showing 3q amplification by aCGH (+3q25.3-3q27.3) showed ≥8 fluorescent signals at FISH evidencing a 3q/3 ratio >2. The remaining cases showed flat genomic portrait at aCGH on chromosome 3. We concluded that: 1) absolute copy number of 3q chromosomal region may harbour false positive interpretation of 3q amplification in squamous cell carcinoma; 2) a case results truly "amplified for chromosome 3q" when showing ≥8 fluorescent 3q signals; 3) trials involving drugs targeting loci on chromosome 3q in squamous lung carcinoma therapy have to consider false versus true 3q chromosomal amplification.

Colorectal cancer treatment in elderly patients: an update on recent clinical studies.

Colorectal cancer (CRC) is one of the most common cancers in the Western world, with > 500,000 new cases diagnosed each year. One of the strongest risk factors for colon cancer is age. Physicians and their older patients commonly face the dilemma of whether to give/receive systemic chemotherapy for CRC. Evidence supports similar survival benefits with adjuvant and palliative chemotherapy in elderly patients compared with younger age groups. Data on treatment- related side effects did not reveal a different toxicity profile for elderly patients. The safety and efficacy of systemic chemotherapy in fit older patients were proven, and this group of patients could be enrolled in clinical trials. Conversely, frail older patients are more likely to suffer adverse outcomes when faced with stressors and might not benefit from chemotherapy. Despite a growing body of data, a great deal of work is still needed to establish optimal strategies to care for patients diagnosed with cancer later in life. There is a paucity of reports published in the literature because of the difficulty in routinely collecting such data. We report an overview of recent studies (clinical trials, pooled analysis, and population studies) to provide more information and to identify new and better treatment options.

Utility of 18F-FDG PET and contrast-enhanced CT scan in the assessment of residual liver metastasis from colorectal cancer following adjuvant chemotherapy.

BACKGROUND: Neoadjuvant chemotherapy has been successfully used in the treatment of patients with colorectal liver metastases. The selection of patients for surgical resection after chemotherapy still poses a significant clinical challenge. (18)F-FDG PET is a useful tool in the assessment of liver metastases but the data regarding its sensitivity after chemotherapy is scarce. Our aim was to assess the value of this imaging modality in the selection of patients with colorectal liver metastasis for surgery following adjuvant chemotherapy. MATERIAL AND METHODS: We reviewed the diagnostic performances of (18)F-FDG PET and contrast-enhanced CT scan data from patients with colorectal liver metastases following treatment with chemotherapy. Nineteen patients (12 males, 7 females; median age 61 years; range 41-79) were evaluated. Chemotherapy regimens were: FOLFOX (14 patients), FOLFIRI (3 patients), 5-FU/FA (1 patient) and UFT-irinotecan-oxaliplatin (1 patient). Median time between end of chemotherapy and CT scan was 3.4 weeks, between end of chemotherapy and PET was 5.9 weeks and between end of chemotherapy and surgery was 9.9 weeks. All patients underwent surgery and had histopathological confirmation of liver lesions. Nine patients had segmentectomy, 2 patients had wedge resection, 5 patients had right hepatectomy and 3 patients had explorative laparotomy with liver biopsies. RESULTS: Data from all 19 patients, comprising 65 liver lesions, were confirmed by histo-pathology. Results on a per-lesion basis showed a sensitivity of 62% for (18)F-FDG PET and 70% for CT scan. A complete agreement between (18)F-FDG PET or CT scan and histology was documented in 5 and 3 patients, respectively. The sensitivity of (18)F-FDG PET was shown to increase for lesions larger than 1 cm (74% vs. 18%). CONCLUSIONS: These results suggest that (18)F-FDG PET and CT scan have sub-optimal sensitivity in the evaluation of colorectal liver lesions after neo-adjuvant chemotherapy, especially for lesions < 1 cm. The combined use of the two imaging techniques does not significantly increase the sensitivity of lesion detection.

Oral ulcer as an exclusive sign of gastric cancer: report of a rare case.

BACKGROUND: The oral cavity is a rare but occasional target for metastases, which may masquerade as various benign and inflammatory lesions, and sometimes also be asymptomatic. Oral metastatic lesions have been described in various cancers, particularly lung, breast and kidney carcinoma. CASE PRESENTATION: We here describe an uncommon case of a hard palate mucosa and gingival metastasis from gastric carcinoma that was originally diagnosed as a periodontal disease. Histopathological examination of a biopsy of the lesion revealed a signet-ring cell carcinoma, and a subsequent biopsy of an ulcerated stomach lesion showed a poorly differentiated gastric carcinoma. The patient underwent gastric resection but died of heart failure on the tenth postoperative day; a post-mortem examination revealed a residual bilateral ovarian infiltration by gastric carcinoma (Krukenberg's tumor). CONCLUSION: An occult carcinoma of the stomach may rarely metastasise to the oral cavity even as a first and exclusive manifestation; it is important to bear this possibility in mind because such conditions may mimic a benign disease.