Publications by authors named "Graziella Pinotti"

71 Publications

Management of patients with cancer during the COVID-19 pandemic: The Italian perspective on the second wave.

Eur J Cancer 2021 Feb 25;148:112-116. Epub 2021 Feb 25.

Medical Oncology Unit, ARNAS Civico, Palermo, Italy.

The novel coronavirus disease 2019 (COVID-19) pandemic has been an overwhelming challenge for worldwide health systems. Since the beginning of year 2020, COVID-19 has represented a potential harm for cancer patients and has often hindered oncology care. The Collegio Italiano dei Primari Oncologi Medici (CIPOMO) is an Italian association of head physicians in oncology departments, which promotes working and research activities in oncology on a national basis. During the second wave of COVID-19 pandemic, the CIPOMO promoted a national survey aiming to evaluate the impact of COVID-19 on oncologists' clinical activity and what changes have been made compared with the Italian situation during the first wave of the pandemic. Overall, 138 heads of medical oncology departments participated in this survey: 75 (54%) from the North, 24 (17%) from the Centre and 39 (28%) from the South of Italy and islands. This survey provides an overview of Italian oncologists facing the second wave of COVID-19 pandemic. The lesson learned during the first wave of COVID-19 pandemic has led to a better organisation of clinical activities, and regular testing among healthcare practitioners, with better chances to grant patients' protection. However, the lack of standardised informatic platforms results in serious challenges in replacing frontal visits, often making a concrete reduction of patients' hospital accesses unfeasible. Oncologists need to keep preserving the continuum of care of patients. Standardisation of safety measures, together with the implementation of informatic platforms, can significantly improve oncology pathways during this second wave of COVID-19 pandemic.
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http://dx.doi.org/10.1016/j.ejca.2021.01.040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904514PMC
February 2021

Effect Modifiers of Low-Dose Tamoxifen in a Randomized Trial in Breast Noninvasive Disease.

Clin Cancer Res 2021 Feb 19. Epub 2021 Feb 19.

IEO, European Institute of Oncology IRCCS, Milan, Italy.

Purpose: Low-dose tamoxifen halved recurrence after surgery in a phase III trial in breast noninvasive disease without increasing adverse events. We explored the effect of low-dose tamoxifen in clinically relevant subgroups, including menopausal status, estradiol levels, smoking, body mass index, and proliferation of baseline lesion.

Patients And Methods: Incidence of invasive breast cancer or ductal carcinoma was the primary endpoint. HRs and interaction terms were estimated using Cox models.

Results: A favorable HR and 95% confidence interval (CI) could be demonstrated for postmenopausal status (HR = 0.30; 95% CI, 0.11-0.82 vs. HR = 0.73; 95% CI, 0.30-1.76 in premenopausal women; = 0.13), women with estradiol less than 15.8 pg/mL, presence of menopausal symptoms at baseline, and never smoking ( = 0.07), although the interaction value was >0.05 for all characteristics. Efficacy was similar in all body mass index categories. Tumors with Ki-67 above the median level of 10% had a greater benefit (HR = 0.27; 95% CI, 0.09-0.81) than those with Ki-67 ≤10% (HR = 1.58; 95% CI, 0.45-5.60; = 0.04).

Conclusions: The efficacy of low-dose tamoxifen seems to be greater in postmenopausal women and in women with lower estradiol levels. Benefits appear to be larger also in women with menopausal symptoms, never smokers, and tumors with Ki-67 >10%. Our results by menopausal status provide important insight into low-dose tamoxifen personalized treatment, although caution is necessary given their exploratory nature. Observation of an improved response in tumors with Ki-67 >10% is consistent but the use of the marker in this setting is investigational.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-4213DOI Listing
February 2021

Combination of radiation therapy for brain metastasis and anti-PD-1/PD-L1 treatment in non-small cell lung cancer: two cases and review of the literature.

Anticancer Drugs 2021 Apr;32(4):460-464

Medical Oncology Department, ASST Sette Laghi, Ospedale di Circolo.

Lung cancer is the most frequent cause of cancer-related death worldwide and is usually diagnosed in advanced stages. Among those, approximately 7.4% of non-small cell lung cancer (NSCLC) patients will have brain metastasis (BM) at presentation, and 25-30% will develop BM during the course of their disease. To date, patients with BMs are increasingly considered for combined treatment using systemic immune checkpoint inhibition (ICI) and cranial radiation therapy (RT); yet, there is limited data regarding the safety of this approach. Here, we report two cases of NSCLC patients treated with two different types of cranial RT and ICIs.
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http://dx.doi.org/10.1097/CAD.0000000000000996DOI Listing
April 2021

Overall Survival in Metastatic Breast Cancer Patients in the Third Millennium: Results of the COSMO Study.

Clin Breast Cancer 2020 Nov 9. Epub 2020 Nov 9.

Department of Oncology, ASST Bergamo Ovest Ospedale di Treviglio, Treviglio, Italy.

Introduction: Metastatic breast cancer (MBC) is a life-threatening disease, and although some data suggest a trend in survival improvement, it has not yet been unequivocally demonstrated. This study aimed to evaluate the overall survival (OS) of MBC patients, assessing its correlation with prognostic factors.

Patients And Methods: COSMO (Checking Overall Survival in a MBC Observational study) is an Italian longitudinal retrospective multicenter study that enrolled patients with MBC diagnosed between 2000 and 2008. The primary objective was to detect a temporal difference in OS; the secondary objective was to identify prognostic factors as causal factors of the temporal variation in OS.

Results: A total of 3721 of 3930 patients from 31 centers were distributed in 3 periods: 886 (23.8%), 1302 (35.0%), and 1533 (41.2%) in 2000-2002, 2003-2005, and 2006-2008, respectively. With a median follow-up of 9.3 years, median OS was 2.8 years (95% confidence interval, 2.6-2.9). No difference in OS was found in the 3 cohorts (P for trend = .563). The worst prognosis was observed for patients with triple-negative MBC (OS, 1.5 years) and for those with central nervous system metastases (1.7 years); the best prognosis was observed in those with bone metastases or nonvisceral disease (3.4 and 3.2 years, respectively) and in patients with a disease-free interval, defined as the time between resection of the primary malignancy and diagnosis of MBC, of > 2 years (3 years).

Conclusions: The COSMO study found improvement in OS between 2000 and 2008. Molecular subtype remained the strongest prognostic factor, and the role of other prognostic factors was confirmed, in particular disease-free interval, site of metastasis, and age.
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http://dx.doi.org/10.1016/j.clbc.2020.11.001DOI Listing
November 2020

Long-term therapy with Bevacizumab in a young patient affected by NF2. Stop or continue treatment? An update of a case report and review of the literature.

Anticancer Drugs 2020 08;31(7):754-757

Medical Oncology, ASST Sette Laghi, Ospedale di Circolo e Fondazione Macchi.

Neurofibromatosis type 2 (NF2) is an autosomal dominant condition caused by pathogenic variants in the NF2 gene. To date, cytotoxic chemotherapy has no established role in the treatment of NF-2. Historical case reports of malignant schwannomas have documented responses to chemotherapies with cyclophosphamide, vincristine and doxorubicin, in patients who develop pulmonary metastases. Recently, several studies proposed the use of anti-HER2, anti-EGFR, anti-platelet-derived growth factor receptors. As reported in our previous review of the literature, vascular endothelial growth factor (VEGF) and its receptor VEGFR-1 have been detected in schwannomas with the best results. We described the case of a young patient with NF2 treated for long time with Bevacizumab. Here, we report the update of the previous case report.
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http://dx.doi.org/10.1097/CAD.0000000000000953DOI Listing
August 2020

When primary hyperparathyroidism comes as good news.

Endocrinol Diabetes Metab Case Rep 2020 Jun 4;2020. Epub 2020 Jun 4.

Department of Medicine and Surgery, Endocrine Unit, University of Insubria, Varese, Italy.

Summary: Brown tumors are osteoclastic, benign lesions characterized by fibrotic stroma, intense vascularization and multinucleated giant cells. They are the terminal expression of the bone remodelling process occurring in advanced hyperparathyroidism. Nowadays, due to earlier diagnosis, primary hyperparathyroidism keeps few of the classical manifestations and brown tumors are definitely unexpected. Thus, it may happen that they are misdiagnosed as primary or metastatic bone cancer. Besides bone imaging, endocrine evaluation including measurement of serum parathyroid hormone and calcium (Ca) levels supports the pathologist to address the diagnosis. Herein, a case of multiple large brown tumors misdiagnosed as a non-treatable osteosarcoma is described, with special regards to diagnostic work-up. After selective parathyroidectomy, treatment with denosumab was initiated and a regular follow-up was established. The central role of multidisciplinary approach involving pathologist, endocrinologist and oncologist in the diagnostic and therapeutic work-up is reported. In our opinion, the discussion of this case would be functional especially for clinicians and pathologists not used to the differential diagnosis in uncommon bone disorders.

Learning Points: Brown tumors develop during the remodelling process of bone in advanced and long-lasting primary or secondary hyperparathyroidism. Although rare, they should be considered during the challenging diagnostic work-up of giant cell lesions. Coexistence of high parathyroid hormone levels and hypercalcemia in primary hyperparathyroidism is crucial for the diagnosis. A detailed imaging study includes bone X-ray, bone scintiscan and total body CT; to rule out bone malignancy, evaluation of bone lesion biopsy should include immunostaining for neoplastic markers as H3G34W and Ki67 index. If primary hyperparathyroidism is confirmed, selective parathyroidectomy is the first-line treatment. In advanced bone disease, treatment with denosumab should be considered, ensuring a strict control of Ca levels.
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http://dx.doi.org/10.1530/EDM-20-0046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354736PMC
June 2020

Late immune-related adverse events in long-term responders to PD-1/PD-L1 checkpoint inhibitors: A multicentre study.

Eur J Cancer 2020 07 23;134:19-28. Epub 2020 May 23.

Department of Dermatology, St. Salvatore Hospital, L'Aquila, Italy; Medical Oncology, St. Salvatore Hospital, L'Aquila, Italy.

Background: Data on spectrum and grade of immune-related adverse events (irAEs) in long-term responders to immune checkpoint inhibitors (ICIs) are lacking.

Methods: We performed a retrospective multicenter study to characterized irAEs occurring after a 12-months minimum treatment period with PD-(L)1 ICIs in patients with advanced cancer. IrAEs were categorized into 'early' (≤12 months) and 'late' (>12 months).

Results: From September 2013 to October 2019, 436 consecutive patients were evaluated. Two hundred twenty-three experienced any grade early-irAEs (51.1%), whereas 132 experienced any grade late-irAEs (30.3%) (p < 0.0001). Among the latter, 29 (22%) experienced a recurrence of an early-irAEs, whereas 103 (78%) experienced de novo late-irAEs involving different system/organ. Among patients with late-irAEs, 21 experienced GIII/GIV irAEs (4.8%). Median time to onset of early-irAEs was 3.4 months (95% confidence interval [CI]: 2.8-4.2), whereas the median time to onset of late-irAEs was 16.6 months (95% CI: 15.8-17.6). Cumulative time-adjusted risk of disease progression according to both the early-irAEs (hazard ratio [HR] = 0.63 [95% CI: 0.30-1.29], p = 0.204) and late-irAEs occurrence revealed no statistically significant differences (HR = 0.75 [95% CI: 0.37-1.56], p = 0.452). In addition, the time-adjusted cumulative risk of death in accordance with both early-irAEs (HR = 0.79 [95% CI: 0.34-1.86], p = 0.598) and late-irAEs (HR = 0.92 [95% CI: 0.49-1.74], p = 0.811) did not show statistically significant differences.

Conclusion: Although less frequent than early-irAEs, late-irAEs are quite common in long responders to PD-(L)1 ICIs and are different in terms of spectrum and grade. Time-adjusted analysis revealed that the cumulative risk of disease progression and death were not significantly reduced in patients who experienced late-irAEs.
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http://dx.doi.org/10.1016/j.ejca.2020.04.025DOI Listing
July 2020

Psoriatic arthritis induced by anti-PD1 and treated with apremilast: a case report and review of the literature.

Immunotherapy 2020 06 22;12(8):549-554. Epub 2020 Apr 22.

Humanitas Clinical and Research Center -IRCCS-, Rozzano, Italy.

Immune checkpoint inhibitors targeting programmed cell death protein 1 pathways are generally well tolerated, but immune-related adverse events have been observed in more than 80% of all patients. Rheumatic and musculoskeletal immune related adverse events have to date not been widely recognized or well characterized. Psoriasic arthritis is a rare entity and it makes management of patients difficult due to the limited therapeutic possibilities and the strong impact on the quality of life. The majority of cases were treated with glucocorticoids, in some cases not enough. We present the case of a patient with psoriasic arthritis and report cases described in literature of patients treated with apremilast, a small oral molecule that inhibits of phosphodiestherase 4.
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http://dx.doi.org/10.2217/imt-2019-0085DOI Listing
June 2020

Reorganisation of medical oncology departments during the novel coronavirus disease-19 pandemic: a nationwide Italian survey.

Eur J Cancer 2020 06 6;132:17-23. Epub 2020 Apr 6.

Medical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

The novel severe acute respiratory syndrome coronavirus-2 pandemic is a global health problem, which started to affect China by the end of 2019. In Europe, Italy has faced this novel disease entity (named novel coronavirus disease [COVID-19]) first and severely. COVID-19 represents a significant hurdle for public health services and a potential harm for patients with cancer. The Collegio Italiano dei Primari Oncologi Medici (CIPOMO) is an Italian association of head physicians in oncology departments, which promotes working and research activities in oncology on a national basis. In the midst of the epidemic in Italy, the CIPOMO promoted a national survey aiming to evaluate the impact of COVID-19 on clinical activity of oncologists and the implementation of containment measures of COVID-19 diffusion. Overall, 122 head physicians participated in this survey, with a homogeneous distribution on the national territory. Results show that the following measures for oncologic patients have been promptly implemented through the whole country: use of protective devices, triage of patients accessing the hospital, delay of non-urgent visits and use of telemedicine. Results of this survey suggest that Italian oncology departments have promptly set a proactive approach to the actual emergency. Oncologists need to preserve the continuum of care of patients, as the benefit of ensuring a well-delivered anti-cancer treatment plan outweighs the risk of COVID-19 infection. International cooperation is an important starting point, as heavily affected nations can serve as an example to find out ways to safely preserve health activity during the pandemic.
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http://dx.doi.org/10.1016/j.ejca.2020.03.024DOI Listing
June 2020

Will traditional biopsy be substituted by radiomics and liquid biopsy for breast cancer diagnosis and characterisation?

Med Oncol 2020 Mar 16;37(4):29. Epub 2020 Mar 16.

Breast Imaging Division, IEO European Institute of Oncology IRCCS, Via Giuseppe Ripamonti, 435, 20141, Milan, MI, Italy.

The diagnosis of breast cancer currently relies on radiological and clinical evaluation, confirmed by histopathological examination. However, such approach has some limitations as the suboptimal sensitivity, the long turnaround time for recall tests, the invasiveness of the procedure and the risk that some features of target lesions may remain undetected, making re-biopsy a necessity. Recent technological advances in the field of artificial intelligence hold promise in addressing such medical challenges not only in cancer diagnosis, but also in treatment assessment, and monitoring of disease progression. In the perspective of a truly personalised medicine, based on the early diagnosis and individually tailored treatments, two new technologies, namely radiomics and liquid biopsy, are rising as means to obtain information from diagnosis to molecular profiling and response assessment, without the need of a biopsied tissue sample. Radiomics works through the extraction of quantitative peculiar features of cancer from radiological data, while liquid biopsy gets the whole of the malignancy's biology from something as easy as a blood sample. Both techniques hopefully will identify diagnostic and prognostic information of breast cancer potentially reducing the need for invasive (and often difficult to perform) biopsies and favouring an approach that is as personalised as possible for each patient. Nevertheless, such techniques will not substitute tissue biopsy in the near future, and even in further times they will require the aid of other parameters to be correctly interpreted and acted upon.
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http://dx.doi.org/10.1007/s12032-020-01353-1DOI Listing
March 2020

Cyclin-dependent kinase inhibitors plus aromatase inhibitor in first-line treatment hormone-receptor-positive/HER2-negative advanced breast cancer women with or without visceral disease: time to turn page?

Anticancer Drugs 2020 06;31(5):528-532

Medical Oncology, ASST-Settelaghi, Ospedale di Circolo e Fondazione Macchi, Varese, Italy.

Breast cancer is the most common female tumour type and accounts for the leading cancer mortality in women worldwide. Up to 75% of breast cancers express the oestrogen receptor or progesterone receptor (hormone-receptor-positive). Aromatase inhibitors were the preferred first-line treatment option. New and acquired resistance to hormonal blockade has led to the development of targeted treatments. Cyclin-dependent kinases (CDKs) are a large family of serine-threonine kinases that play an important role in regulating cell cycle progression: palbociclib, ribociclib, and abemaciclib. We conducted a study to evaluate the efficacy of CDK inhibitors (CDKi) plus aromatase inhibitor in hormone-receptor-positive/HER2-negative ABC patients with visceral disease, postponing the use of chemotherapeutic agents and strengthening the power of endocrine agents. We enrolled 22 patients treated with CDKi (palbocilib) plus aromatase inhibitor (group A) and 38 patients treated with chemotherapy (group B). Our small study confirms the effectiveness of treatment with CDKi plus aromatase inhibitor, even in patients with visceral metastases, when compared with chemotherapy.
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http://dx.doi.org/10.1097/CAD.0000000000000904DOI Listing
June 2020

On-target Toxicities Predictive of Survival in Metastatic Renal Cell Carcinoma (mRCC) Treated With Sunitinib: A Multicenter Retrospective Study.

Clin Genitourin Cancer 2020 04 5;18(2):e145-e156. Epub 2019 Dec 5.

Dipartimento di Medicina e Chirurgia, Università degli Studi dell'Insubria di Varese, Varese, Italy.

Background: Preliminary studies suggested that selected drug-related toxicities of sunitinib may correlate with a better prognosis.

Patients And Methods: From January 2006 through December 2015, we retrospectively analyzed data of 145 patients with metastatic renal cell carcinoma treated with sunitinib as a first-line therapy in 7 different Italian oncology departments. Hypertension, hypothyroidism, thrombocytopenia, neutropenia, and anemia were evaluated. Overall survival (OS) and progression-free survival (PFS) were calculated. OS and PFS were compared in patients who developed and who did not develop a drug-related toxicity. A multivariate analysis using the Cox regression model was performed.

Results: We evaluated 145 patients (92 males; median age, 70 years); 105 (62.4%) patients experienced at least 1 toxicity: 66 (45.5%) patients developed hypothyroidism, 41 (28.3%) thrombocytopenia, 39 (26.9%) hypertension that required medical therapy, 22 (15.2%) anemia, and 11 (7.6%) neutropenia. The median PFS of patients who developed hypertension was 12 months (95% confidence interval [CI], 9-21 months) versus 9 months (95% CI, 7-12 months) in patients who did not develop toxicity; the median OS was 36 months (95% CI, 22 months to not reached) versus 26 months (95% CI, 18-34 months). For neutropenia, the median PFS was 17.5 months (95% CI, 9-65 months) versus 10 months (95% CI, 8-12 months); the median OS was 23 months (95% CI, 13 months to not reached) versus 28 months (95% CI, 22-35 months). At univariate and multivariate analysis, we observed a protective effect of hypertension and neutropenia on tumor progression (hazard ratio, 0.47; 95% CI, 0.28-0.78 and hazard ratio, 0.26; 95% CI, 0.09-0.76, respectively).

Conclusions: Many patients developed toxicities during treatment with sunitinib; hypertension and neutropenia were related to longer PFS in our cohort.
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http://dx.doi.org/10.1016/j.clgc.2019.10.003DOI Listing
April 2020

T790M detection rate in lung adenocarcinomas at baseline using droplet digital PCR and validation by ultra-deep next generation sequencing.

Transl Lung Cancer Res 2019 Oct;8(5):584-592

Unit of Pathology, Department of Medicine and Surgery, ASST Sette Laghi, University of Insubria, Varese, Italy.

Background: Routine testing of baseline T790M mutation may have important clinical impact but many discordant data have been reported regarding the diagnostic, prognostic and predictive role of this marker. In this study we aimed to assess T790M frequency in 164 untreated -mutated NSCLCs using methods with different sensitivity as well as to analyze the relationship between baseline T790M mutation status, patient's clinicopathologic features and tyrosine kinase inhibitors (TKI) treatment outcomes.

Methods: We compared the diagnostic performance, sensitivity and specificity of three methods, namely MALDI-TOF mass spectrometry (MS), Allele-Specific Real Time PCR (AS-PCR), droplet digital PCR (ddPCR). Ultra-deep next generation sequencing (NGS) validation of T790M-mutant NSCLCs was performed using SiRe panel.

Results: Baseline T790M occurred in 17% of the tumors. Intermediately sensitive techniques such as MALDI-TOF MS (detection limit of T790M ≥5%) allow to detect T790M in 2% of cases exhibiting mutant-allele fractions ranging from 11.5% to 17%. Median overall survival (OS) in these patients was poor (7.3 months) and progression free survival (PFS) was of 3.3 months in patients treated with a 1st generation EGFR TKI. The remaining T790M-positive cases showed very low mutant-allele fractions ranging from 0.07% to 0.38% and required highly sensitive methods such as ddPCR and NGS to be identified. All these cases showed a concurrent sensitizing mutation (mainly exon 19 deletion), and clinicopathological features similar to those observed in mutant cancers. Median OS of these patients was 27 months while median PFS after TKI treatment was 20 months.

Conclusions: Routine test of baseline T790M may have an important role in the prediction to EGFR TKI therapy response and should be performed using highly sensitive and quantitative methods, such as ddPCR and NGS, in order to reliably distinguish NSCLCs with high or very low T790M mutant-allele fraction.
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http://dx.doi.org/10.21037/tlcr.2019.09.18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6835109PMC
October 2019

Absolute Improvements in Freedom From Distant Recurrence to Tailor Adjuvant Endocrine Therapies for Premenopausal Women: Results From TEXT and SOFT.

J Clin Oncol 2020 04 16;38(12):1293-1303. Epub 2019 Oct 16.

International Breast Cancer Study Group Statistical Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.

Purpose: The Tamoxifen and Exemestane Trial (TEXT)/Suppression of Ovarian Function Trial (SOFT) showed superior outcomes for premenopausal women with hormone receptor (HR)-positive breast cancer treated with adjuvant exemestane plus ovarian function suppression (OFS) or tamoxifen plus OFS versus tamoxifen alone. We previously reported the magnitude of absolute improvements in freedom from any recurrence across a continuous, composite measure of recurrence risk to tailor decision making. With longer follow-up, we now focus on distant recurrence.

Methods: The TEXT/SOFT HR-positive/human epidermal growth factor receptor 2 (HER2)-negative analysis population included 4,891 women stratified by predetermined chemotherapy use. Kaplan-Meier estimates of 8-year freedom from distant recurrence were analyzed using subpopulation treatment effect pattern plot (STEPP) methodology across subpopulations defined by the continuous composite measure of recurrence risk. For each patient, the composite risk value was obtained from a Cox model that incorporated age; nodal status; tumor size; grade; and estrogen receptor, progesterone receptor, and Ki-67 labeling index expression levels.

Results: The overall rate of 8-year freedom from distant recurrence was 91.1% and ranged from approximately 100% to 63% across lowest to highest composite risks. TEXT patients who received chemotherapy had an average absolute improvement with exemestane plus OFS versus tamoxifen plus OFS of 5.1%, and STEPP analysis showed improvements from less than 1% to more than 15% from lowest to highest composite risks. SOFT patients who remained premenopausal after chemotherapy had an average 5.2% absolute improvement with exemestane plus OFS versus tamoxifen and reached 10% across composite risks; for tamoxifen plus OFS versus tamoxifen, the maximum improvement was approximately 3.5%. Women who did not receive chemotherapy had a more than 97% rate of 8-year freedom from distant recurrence, and improvements with exemestane plus OFS ranged from 1% to 4%.

Conclusion: Premenopausal women with HR-positive/HER2-negative breast cancer and high recurrence risk, as defined by clinicopathologic characteristics, may experience a 10% to 15% absolute improvement in 8-year freedom from distant recurrence with exemestane plus OFS versus tamoxifen plus OFS or tamoxifen alone. The potential benefit of escalating endocrine therapy versus tamoxifen alone is minimal for those at low recurrence risk.
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http://dx.doi.org/10.1200/JCO.18.01967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164485PMC
April 2020

Biological effects of verbascoside and its anti-inflammatory activity on oral mucositis: a review of the literature.

Anticancer Drugs 2020 01;31(1):1-5

ASST-Settelaghi, Department of Medical Oncology, Ospedale di Circolo, Varese, Italy.

Oral mucositis is among the most common tissue toxicities associated with both cytotoxic cancer regimens and head and neck radiotherapy. Current management of oral mucositis might comprise growth factors and cytokines, anti-inflammatory agents, anesthetics, analgesics, antimicrobial and coating agents, cryotherapy and mucosal protectants. Despite its long history and its impact on patients, there are currently no effective options for the prevention or treatment of mucositis. In recent years, more attention has been focused on the role of natural drugs. Verbascoside belongs to the phenylpropanoid glycosides family. Several biological properties have been described, such as anti-inflammatory, antimicrobial, antitumor and antioxidant. Verbascoside, particularly when in solution with polyvinylpyrrolidone and sodium hyaluronate, thanks to barrier effect, is useful in re-epithelialization and in reducing pain, oral mucositis score, burning and erythema.
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http://dx.doi.org/10.1097/CAD.0000000000000818DOI Listing
January 2020

Randomized Placebo Controlled Trial of Low-Dose Tamoxifen to Prevent Local and Contralateral Recurrence in Breast Intraepithelial Neoplasia.

J Clin Oncol 2019 07 11;37(19):1629-1637. Epub 2019 Apr 11.

3 European Institute of Oncology IRCCS, Milan, Italy.

Purpose: Tamoxifen administered for 5 years at 20 mg/d is effective in breast cancer treatment and prevention, but toxicity has limited its broad use. Biomarker trials showed that 5 mg/d is not inferior to 20 mg/d in decreasing breast cancer proliferation. We hypothesized that a lower dose given for a shorter period could be as effective in preventing recurrence from breast intraepithelial neoplasia but have a lower toxicity than the standard dose.

Patients And Methods: We conducted a multicenter randomized trial of tamoxifen, 5 mg/d or placebo administered for 3 years after surgery in women with hormone-sensitive or unknown breast intraepithelial neoplasia, including atypical ductal hyperplasia and lobular or ductal carcinoma in situ. The primary end point was the incidence of invasive breast cancer or ductal carcinoma in situ.

Results: Five hundred women 75 years of age or younger were included. After a median follow-up of 5.1 years (interquartile range, 3.9-6.3 years), there were 14 neoplastic events with tamoxifen and 28 with placebo (11.6 23.9 per 1,000 person-years; hazard ratio, 0.48; 95% CI, 0.26 to 0.92; = .02), which resulted in a 5-year number needed to treat of 22 (95% CI, 20 to 27). Tamoxifen decreased contralateral breast events by 75% (three 12 events; hazard ratio, 0.25; 95% CI, 0.07 to 0.88; = .02). Patient-reported outcomes were not different between arms except for a slight increase in frequency of daily hot flashes with tamoxifen ( = .02). There were 12 serious adverse events with tamoxifen and 16 with placebo, including one deep vein thrombosis and one stage I endometrial cancer with tamoxifen and one pulmonary embolism with placebo.

Conclusion: Tamoxifen at 5 mg/d for 3 years can halve the recurrence of breast intraepithelial neoplasia with a limited toxicity, which provides a new treatment option in these disorders.
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http://dx.doi.org/10.1200/JCO.18.01779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6601429PMC
July 2019

Assessment of Ramucirumab plus paclitaxel as switch maintenance versus continuation of first-line chemotherapy in patients with advanced HER-2 negative gastric or gastroesophageal junction cancers: the ARMANI phase III trial.

BMC Cancer 2019 Mar 29;19(1):283. Epub 2019 Mar 29.

Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, via G. Venezian, 1, 20133, Milan, Italy.

Background: Platinum/fluoropyrimidine regimens are the backbone of first-line chemotherapy for advanced gastric cancer (AGC). However response rates to first line chemotherapy range from 30 to 50% and disease progression occurs after 4-6 cycles. The optimal duration of first-line therapy is still unknown and its continuation until disease progression represents the standard. However this strategy is often associated with cumulative toxicity and rapid development of drug resistance. Moreover, only about 40% of AGC pts. are eligible for second-line treatment.

Methods: This is a randomized, open-label, multicenter phase III trial. It aims at assessing whether switch maintenance to ramucirumab plus paclitaxel will extend the progression-free survival (PFS) of subjects with HER-2 negative AGC who have not progressed after 3 months of a first-line with a platinum/fluoropyrimidine regimen (either FOLFOX4, mFOLFOX6 or XELOX). The primary endpoint is to compare Progression-Free Survival (PFS) of patients in ARM A (switch maintenance to ramucirumab and placlitaxel) versus ARM B (continuation of the same first-line therapy with oxaliplatin/fluoropyrimidine). Secondary endpoints are: overall survival, time-to-treatment failure, overall response rate, duration of response, percentage of patients that will receive a second line therapy according to arm treatment, safety, quality of life. Exploratory studies including Next-Generation Sequencing (NGS) in archival tumor tissues are planned in order to identify potential biomarkers of primary resistance and prognosis.

Discussion: The ARMANI study estimates if patients treated with early swich with ramucirumab plus paclitaxel received benefit when compared to those treated with continuation of first line therapy. The hypothesis is that the early administration of an active, non-cross resistant second-line regimen such as ramucirumab plus paclitaxel may prolong the time in which patients are progression-free, and consequently have a better quality of life. Moreover, this strategy may rescue all those subjects that become ineligible for second-line therapy due to the rapid deterioration of health status after the first disease progression.

Trial Registration: ARMANI is registered at ClinicalTrials.gov ( NCT02934464 , October 17, 2016) and EudraCT(2016-001783-12, April 202,016).
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http://dx.doi.org/10.1186/s12885-019-5498-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440108PMC
March 2019

Nivolumab and brain metastases in patients with advanced non-squamous non-small cell lung cancer.

Lung Cancer 2019 03 15;129:35-40. Epub 2019 Jan 15.

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.

Objectives: Brain metastases are common among patients with non-squamous non-small-cell lung cancer (NSCLC) and result in a poor prognosis. Consequently, such patients are often excluded from clinical trials. In Italy an expanded access program (EAP) was used to evaluate nivolumab efficacy and safety in this subpopulation outside a clinical trial.

Materials And Methods: In this EAP, nivolumab was available for patients with non-squamous NSCLC in progression after at least one systemic treatment for stage IIIB/IV disease. Nivolumab 3 mg/kg was administered intravenously every 2 weeks. Patients with brain metastases could be included if they were asymptomatic, neurologically stable and either off corticosteroids or on a stable or decreasing dose of ≤10 mg/day prednisone.

Results: 409 out of 1588 patients included had asymptomatic or controlled brain metastases. A median of 7 doses (range 1-45) were delivered. Median follow-up was 6.1 months (range 0.1-21.9). The disease control rate was 39%: 4 patients had a complete response, 64 a partial response and 96 showed stable disease. At baseline, 118 patients were on corticosteroids and 74 were undergoing concomitant radiotherapy. The median overall survival in this subpopulation was 8.6 months (95% CI: 6.4-10.8). 337 discontinued treatment for various reasons, 23 (7%) of whom due to adverse events, in line with that observed in the overall population and in previous studies.

Conclusions: Our results confirm that nivolumab is active in non-squamous NSCLC patients with brain metastases, despite their poor prognosis. Its safety profile is also concordant with results in the EAP overall population and in patients with other malignancies.
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http://dx.doi.org/10.1016/j.lungcan.2018.12.025DOI Listing
March 2019

Long-term therapy with bevacizumab in a young patient affected by NF-2: a case report and review of the literature.

Anticancer Drugs 2019 03;30(3):318-321

Department of Medical Oncology, ASST-Settelaghi, Circolo's Hospital, Varese, Italy.

Neurofibromatosis type 2 (NF-2) is an autosomal dominant inherited disease caused by heterozygous mutations in the NF-2 tumor suppressor gene. It is characterized by the development of multiple benign tumors in the central nervous system. A majority of these tumors can be treated with surgery or radiotherapy in the case of the symptomatic disease. Cytotoxic chemotherapy has no established role in the treatment of NF-2. Vascular endothelial growth factor (VEGF) is a critical mediator of tumor angiogenesis and vessel permeability. VEGF and its receptor VEGFR-1 have been detected in schwannomas, and increased levels of these factors correlate with increased rates of tumor growth. The use of bevacizumab has made many progresses in recent years in NF-2 patients. We report a case of a young patient treated with more than 100 administration of bevacizumab, with clinical and instrumental benefits.
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http://dx.doi.org/10.1097/CAD.0000000000000732DOI Listing
March 2019

Rectovaginal fistula during treatment with axitinib in a patient with renal cell carcinoma: a case report and review of the literature.

Anticancer Drugs 2019 04;30(4):425-427

Department of Medical Oncology, ASST-Settelaghi, Circolo Hospital, Varese, Italy.

Renal cell carcinoma (RCC) is one of the most frequent malignancies of the adults. Its incidence has been increasing steadily by 2-4% each year. Up to 30% of patients present with metastases at diagnosis. It is a highly vascularized cancer because of the hypoxia-induced factor stabilization as a consequence of von Hippel-Lindau inactivation. Hypoxia-induced factor accumulation leads to transactivation of molecules involved in angiogenesis including vascular endothelial growth factor (VEGF) and platelet-derived growth factor. Sunitinib is an oral tyrosine kinase inhibitor that interacts with several angiogenesis receptors including platelet-derived growth factor receptors and VEGF receptors, and is approved for the first-line treatment in metastatic RCC. In terms of tolerability, patients treated with sunitinib showed a higher incidence of diarrhea, vomiting, hypertension, hand-foot syndrome, and neutropenia, a safety profile consistent with what had been observed in earlier phase studies. Axitnib is a potent and selective tyrosine kinase inhibitor of VEGF receptors 1, 2, and 3, and is approved in the second-line setting for patients with metastatic RCC. The tolerability profile of axitinib is favorable. The most commonly reported treatment-related adverse events are diarrhea, hypertension, fatigue, nausea, and dysphonia. Bowel toxicity, especially pneumatosis intestinalis and bowel perforation, is very uncommon. In particular, the incidence of intestinal perforation or fistulae is not well known for sunitinib or axitinib. Here, for the first time, we report the incidence of rectovaginal fistula in a 57-year-old White woman, with RCC, following treatment with sunitinib and axitinib.
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http://dx.doi.org/10.1097/CAD.0000000000000742DOI Listing
April 2019

Neuroendocrine Differentiation, Microsatellite Instability, and Tumor-infiltrating Lymphocytes in Advanced Colorectal Cancer With BRAF Mutation.

Clin Colorectal Cancer 2019 06 20;18(2):e251-e260. Epub 2018 Dec 20.

Unit of Pathology, Department of Medicine and Surgery, University of Insubria, Varese, Italy; Research Center for the Study of Hereditary and Familial Tumors, Department of Medicine and Surgery, University of Insubria, Varese, Italy.

Background: Approximately 10% of metastatic colorectal cancer (mCRC) cases will harbor the BRAF p.V600E mutation (BRAF-mCRC) and have been associated with a poor prognosis. Although they are usually considered a unique clinical entity, biologic heterogeneity has been described. We performed an extensive clinicopathologic study of a multicenter series of BRAF-mCRC to highlight differences between tumors with microsatellite instability (MSI) and microsatellite stable tumors, focusing on both inflammatory profiles and neuroendocrine differentiation.

Methods: We included 59 BRAF-mCRC cases and collected the clinical data (ie, surgery, treatment, and follow-up). We evaluated MSI status, budding, lympho-angioinvasion, neuroinvasion, extent of active stroma, CD3 and CD8 intratumoral and peritumoral lymphocytes, programmed cell death ligand 1, p53, Ki-67, synaptophysin, and CDX2 expression.

Results: The 22 MSI BRAF-mCRC cases were associated with the right side (P < .0001), an expansive grown pattern (P < .01), programmed cell death ligand 1 expression (P < .0001), high CD8 T-cell content (P = .0001), and lymph node metastases (P < .029). The 37 MSS BRAF-mCRC cases were characterized by a greater stromal component (P = .0002), pulmonary metastases (P = .095), and p53 and synaptophysin immunoreactivity (P = .004 and P = .001, respectively). Univariate analysis demonstrated that MSI and a high CD8 T-cell content were associated with a 34% (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.34-1.28; P = .2) and 33% (HR, 0.67; 95% CI, 0.45-0.99; P = .04) reduction in the risk of death, respectively. The combined presence of MSI and CD8 T-cell content decreased the hazard of mortality ≤ 63% (HR, 0.37; 95% CI, 0.14-0.97; P = .2), which was slightly reduced after multivariate analysis.

Conclusion: A simultaneous evaluation of MSI, CD8 T-cell content, and neuroendocrine markers could allow for the identification of subsets of BRAF-mCRC with a different prognosis and potential eligibility for specific treatments.
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http://dx.doi.org/10.1016/j.clcc.2018.12.003DOI Listing
June 2019

Primary extranodal diffuse large B-cell lymphomas: Many sites, many entities? Clinico-pathological, immunohistochemical and cytogenetic study of 106 cases.

Cancer Genet 2018 12 28;228-229:28-40. Epub 2018 Aug 28.

Department Of Medicine and Surgery, Unit of Pathology, University of Insubria, Via O. Rossi, 9, 21100 Varese, Italy. Electronic address:

We analyzed the clinicopathological, immunohistochemical and cytogenetic features of 106 extranodal (EN) diffuse large B-cell lymphomas (DLBCLs) from stomach (34 cases), intestine (10), cervico-cephalic region (11), central nervous system (13), testes (21), skin (8), and miscellaneous sites (9). Hans' algorithm and the immunohistochemical double expressor score (DES) for MYC and BCL2 were applied to all cases. A subset of fifty-eight cases were analyzed with fluorescent in situ hybridization (FISH) with specific break apart probes for BCL6, MYC, BCL2, CCND1, BCL10 and MALT1 genes. Clinical records were available for all patients. The immunohistochemical study showed that, in our series of EN-DLBCLs, the Hans' subgroup and the DES differed significantly according to the site of origin. At FISH analysis, BCL6 and BCL2 were the most commonly rearranged genes in non-GC and in GC cases, respectively. Gastrointestinal lymphomas displayed the highest rate of gene rearrangements, often with MYC involvement. One testicular DLBCL showed BCL2/MYC double hit. At survival analysis, cerebral and testicular origin was associated with poor prognosis. In addition, Hans' subgroup and other immunohistochemical markers influenced patients' outcome. In conclusion, our data suggest that immunophenotypic, genetic and survival characteristics of EN-DLBCL are related to the specific primary site of the disease.
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http://dx.doi.org/10.1016/j.cancergen.2018.08.001DOI Listing
December 2018

Isolated diaphragmatic metastasis from resected colorectal cancer.

Dig Liver Dis 2019 03 27;51(3):454. Epub 2018 Sep 27.

Oncology Unit, Ospedale di Circolo, Varese, Italy.

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http://dx.doi.org/10.1016/j.dld.2018.09.020DOI Listing
March 2019

Vitamin D Deficiency has a Negative Impact on Cetuximab-Mediated Cellular Cytotoxicity against Human Colon Carcinoma Cells.

Target Oncol 2018 10;13(5):657-665

Department of Medicine and Surgery, Università degli Studi dell'Insubria, Varese, Italy.

Background: Hypovitaminosis D is associated with an adverse prognosis in colon cancer patients, possibly due to the effects of the vitamin on the immune system. Antibody-dependent cell-mediated cytotoxicity (ADCC) significantly contributes to the anti-tumor effects of monoclonal antibodies, including cetuximab, an epidermal growth factor receptor (EGFR)-targeted monoclonal antibody that is frequently added to chemotherapy in the treatment of colon cancer.

Objective: The present study evaluates the association between vitamin D serum levels and the ability of ex vivo NK cells to support cetuximab-mediated ADCC in colon cancer cell lines.

Methods: Blood samples were obtained from 124 healthy volunteers and serum vitamin D was determined by RIA. NK cells were isolated from each sample and added to human colorectal carcinoma cells with or without cetuximab, and ADCC was assessed using a colorimetric lactate dehydrogenase assay.

Results: Correlation analysis indicates a significant, gender- and age-independent association between vitamin D levels and cetuximab-induced ADCC on HT29 cells, where NK cells from samples with vitamin D < 20 ng/mL are significantly less efficient in inducing ADCC. A confirmatory study on two additional colon cancer cell lines yielded similar results.

Conclusions: These data suggest that vitamin D supplementation in vitamin-deficient/insufficient colorectal cancer patients could improve cetuximab-induced ADCC.
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http://dx.doi.org/10.1007/s11523-018-0586-xDOI Listing
October 2018

Tailoring Adjuvant Endocrine Therapy for Premenopausal Breast Cancer.

N Engl J Med 2018 Jul 4;379(2):122-137. Epub 2018 Jun 4.

From the Peter MacCallum Cancer Centre, St. Vincent's Hospital, University of Melbourne, Melbourne, VIC, and Breast Cancer Trials Australia and New Zealand, University of Newcastle, Newcastle, NSW (P.A.F.), and the University of Sydney, Sydney (A.S.C.) - all in Australia; the Institute of Oncology of Southern Switzerland, Ospedale San Giovanni, Bellinzona (O.P.), Breast Cancer St. Gallen, St. Gallen (T.R.), and the International Breast Cancer Study Group Coordinating Center (R.M., M.R.-P., B.R., A.S.C.), University Hospital Inselspital (M.R.-P.), Bern - all in Switzerland; the University of Chicago Medical Center, Chicago (G.F.F.); the University of Calgary, Calgary, AB, Canada (B.A.W.); the Division of Medical Senology, European Institute of Oncology (M.C.), and the European Institute of Oncology and International Breast Cancer Study Group (A.G.), Milan, Ospedale Papa Giovanni XXIII, Bergamo (C.T.), Azienda Socio Sanitaria Territoriale Sette Laghi-Ospedale di Circolo and Fondazione Macchi, Varese (G.P.), Medical Oncology and Cancer Prevention, IRCCS, National Cancer Institute, Aviano (F.P., S.S.), the Department of Medicine, School of Medical Oncology, University of Udine, Udine (F.P.), Salvatore Maugeri Foundation, Pavia (L.P.), and the Hospital of Prato-Azienda Unità Sanitaria Locale Toscana Centro, Prato (A.D.L.) - all in Italy; the National Institute of Oncology, Budapest, Hungary (I.L.); Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru (H.L.G.); University Hospital 12 de Octubre, Madrid (E.C.), Vall d'Hebron Institute of Oncology and Vall d'Hebron University Hospital, Barcelona (M.B.), and Instituto Valenciano de Oncologia, Valencia (M.A.C.) - all in Spain; the Susan F. Smith Center for Women's Cancers (H.J.B., E.P.W.) and the International Breast Cancer Study Group Statistical Center, Department of Biostatistics and Computational Biology (R.D.G., M.M.R.), Dana-Farber Cancer Institute, Harvard Medical School, the Harvard T.H. Chan School of Public Health, and Frontier Science and Technology Research Foundation (R.D.G.) - all in Boston; Institut Bergonié Comprehensive Cancer Center, Université de Bordeaux, Bordeaux, France (H.R.B., M.D.); the Angeles Clinic and Research Institute, Santa Monica, CA (S.M.); Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond (C.E.G.); Mayo Clinic, Rochester, MN (M.P.G., J.N.I.); Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore (V.S.); Fred Hutchinson Cancer Research Center, University of Washington, Seattle (N.E.D.); Weston Park Hospital, Sheffield, United Kingdom (R.C.); and the Department of Obstetrics and Gynecology, University Medical Center, Regensburg, Germany (S.B.).

Background: In the Suppression of Ovarian Function Trial (SOFT) and the Tamoxifen and Exemestane Trial (TEXT), the 5-year rates of recurrence of breast cancer were significantly lower among premenopausal women who received the aromatase inhibitor exemestane plus ovarian suppression than among those who received tamoxifen plus ovarian suppression. The addition of ovarian suppression to tamoxifen did not result in significantly lower recurrence rates than those with tamoxifen alone. Here, we report the updated results from the two trials.

Methods: Premenopausal women were randomly assigned to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression in SOFT and to receive tamoxifen plus ovarian suppression or exemestane plus ovarian suppression in TEXT. Randomization was stratified according to the receipt of chemotherapy.

Results: In SOFT, the 8-year disease-free survival rate was 78.9% with tamoxifen alone, 83.2% with tamoxifen plus ovarian suppression, and 85.9% with exemestane plus ovarian suppression (P=0.009 for tamoxifen alone vs. tamoxifen plus ovarian suppression). The 8-year rate of overall survival was 91.5% with tamoxifen alone, 93.3% with tamoxifen plus ovarian suppression, and 92.1% with exemestane plus ovarian suppression (P=0.01 for tamoxifen alone vs. tamoxifen plus ovarian suppression); among the women who remained premenopausal after chemotherapy, the rates were 85.1%, 89.4%, and 87.2%, respectively. Among the women with cancers that were negative for HER2 who received chemotherapy, the 8-year rate of distant recurrence with exemestane plus ovarian suppression was lower than the rate with tamoxifen plus ovarian suppression (by 7.0 percentage points in SOFT and by 5.0 percentage points in TEXT). Grade 3 or higher adverse events were reported in 24.6% of the tamoxifen-alone group, 31.0% of the tamoxifen-ovarian suppression group, and 32.3% of the exemestane-ovarian suppression group.

Conclusions: Among premenopausal women with breast cancer, the addition of ovarian suppression to tamoxifen resulted in significantly higher 8-year rates of both disease-free and overall survival than tamoxifen alone. The use of exemestane plus ovarian suppression resulted in even higher rates of freedom from recurrence. The frequency of adverse events was higher in the two groups that received ovarian suppression than in the tamoxifen-alone group. (Funded by Pfizer and others; SOFT and TEXT ClinicalTrials.gov numbers, NCT00066690 and NCT00066703 , respectively.).
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http://dx.doi.org/10.1056/NEJMoa1803164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6193457PMC
July 2018

Poorly Differentiated Neuroendocrine Carcinoma of the Sigmoid Tract in Long-Standing Ulcerative Colitis: Report of a Case and Review of the Literature.

Int J Surg Pathol 2018 Aug 24;26(5):479-483. Epub 2018 Jan 24.

3 university of Insubria, Varese, Italy.

A 37-year-old male with long-standing and extensive ulcerative pancolitis developed a rapidly lethal poorly differentiated neuroendocrine carcinoma (NEC) in the sigmoid colon. Prior biopsies obtained from multiple sites of the colon during endoscopic surveillance showed minimal inflammatory changes and no sign of dysplasia. Patients with inflammatory bowel disease (IBD) are at increased risk of colorectal malignancies, and adenocarcinoma is the most common type of colorectal neoplasm associated with ulcerative colitis and Crohn's disease, but other types of epithelial and nonepithelial tumors have also been described in IBD. NECs arising in the setting of ulcerative colitis are very rare and are reported as anecdotic findings. We describe the clinicopathological features of an IBD-related NEC and review the previously reported cases.
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http://dx.doi.org/10.1177/1066896917752443DOI Listing
August 2018

Outcome of patients older than 80 years with diffuse large B-cell lymphoma (DLBCL) treated with "standard" immunochemotherapy: A large retrospective study from 4 institutions.

Hematol Oncol 2018 Feb 16;36(1):84-92. Epub 2017 Jun 16.

Istituto Oncologico della Svizzera Italiana, Bellinzona, Switzerland.

Little information is available on the very elderly patients with diffuse large B-cell lymphoma (DLBCL). We performed a retrospective analysis of 281 patients >80 years old with newly diagnosed DLBCL treated in 4 referral institutions in Switzerland and Northern Italy. Primary end points were overall survival, progression-free survival, and cause-specific survival. Systemic chemotherapy was given to 239 patients, and 119 of them received rituximab in their initial treatment. At a median follow-up of 5.5 years, 5-year progression-free survival was 26% (95% confidence interval [CI], 20-32%), 5-year overall survival was 31% (95% CI, 25-37%), and 5-year cause-specific survival was 48% (95% CI, 41-55%) for the entire cohort. Rituximab and/or anthracyclines as part of initial treatment were associated with improved outcome. Cause-specific survival in patients receiving both agents approximated 60% at 5 years. At multivariate analysis, rituximab use maintained a significant prognostic impact after controlling for age, performance status, stage, haemoglobin, and lactate dehydrogenase levels. The International Prognostic Index as well as the more recently proposed revised-International Prognostic Index and National Comprehensive Cancer Center Network-International Prognostic Index could discriminate patients with significantly different outcomes. Albeit very elderly and potentially frail, there may be a potential for cure in fit DLBCL patients ≥80 years old. Accurate selection of patients able to tolerate proper immunochemotherapy is crucial.
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http://dx.doi.org/10.1002/hon.2447DOI Listing
February 2018

Biopsy and re-biopsy in lung cancer: the oncologist requests and the role of endobronchial ultrasounds transbronchial needle aspiration.

J Thorac Dis 2017 May;9(Suppl 5):S405-S409

Medical Oncology, ASST Sette Laghi, Varese, Italy.

As the leading cause of death worldwide, lung cancer has proven itself incurable in the advanced stages. For early stages, endobronchial ultrasounds transbronchial needle aspiration (EBUS-TBNA) is now considered the standard to assess mediastinal lymph node, to define the multimodality therapeutic approach. In recent years, EBUS-TBNA has extended its use also in the metastatic and locally recurrent disease. New molecules, with specific mutations that give resistance to current target therapies, have made re-biopsy at disease progression an important assessment, with therapeutic and clinical implication. Here we present the oncologist's point of view on EBUS-TBNA in the staging process, at recurrence and progression.
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http://dx.doi.org/10.21037/jtd.2017.04.09DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5459872PMC
May 2017

ALK-Rearranged Squamous Cell Carcinoma of the Lung Treated with Two Lines of ALK Inhibitors.

J Thorac Oncol 2017 05;12(5):e55-e57

Department of Oncology, Ospedale di Circolo, Varese, Italy.

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http://dx.doi.org/10.1016/j.jtho.2017.01.013DOI Listing
May 2017