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PURPOSE Although representing the majority of newly diagnosed cancers, patients with breast cancer appear less vulnerable to COVID-19 mortality compared with other malignancies. In the absence of patients on active cancer therapy included in vaccination trials, a contemporary real-world evaluation of outcomes during the various pandemic phases, as well as of the impact of vaccination, is needed to better inform clinical practice. METHODS We compared COVID-19 morbidity and mortality among patients with breast cancer across prevaccination (February 27, 2020-November 30, 2020), Alpha-Delta (December 1, 2020-December 14, 2021), and Omicron (December 15, 2021-January 31, 2022) phases using OnCovid registry participants (ClinicalTrials.gov identifier: NCT04393974 ). Twenty-eight-day case fatality rate (CFR28) and COVID-19 severity were compared in unvaccinated versus double-dosed/boosted patients (vaccinated) with inverse probability of treatment weighting models adjusted for country of origin, age, number of comorbidities, tumor stage, and receipt of systemic anticancer therapy within 1 month of COVID-19 diagnosis. RESULTS By the data lock of February 4, 2022, the registry counted 613 eligible patients with breast cancer: 60.1% (n = 312) hormone receptor–positive, 25.2% (n = 131) human epidermal growth factor receptor 2–positive, and 14.6% (n = 76) triple-negative. The majority (61%; n = 374) had localized/locally advanced disease. Median age was 62 years (interquartile range, 51-74 years). A total of 193 patients (31.5%) presented ≥ 2 comorbidities and 69% (n = 330) were never smokers. In total, 392 (63.9%), 164 (26.8%), and 57 (9.3%) were diagnosed during the prevaccination, Alpha-Delta, and Omicron phases, respectively. Analysis of CFR28 demonstrates comparable estimates of mortality across the three pandemic phases (13.9%, 12.2%, 5.3%, respectively; P = .182). Nevertheless, a significant improvement in outcome measures of COVID-19 severity across the three pandemic time periods was observed. Importantly, when reported separately, unvaccinated patients from the Alpha-Delta and Omicron phases achieved comparable outcomes to those from the prevaccination phase. Of 566 patients eligible for the vaccination analysis, 72 (12.7%) were fully vaccinated and 494 (87.3%) were unvaccinated. We confirmed with inverse probability of treatment weighting multivariable analysis and following a clustered robust correction for participating center that vaccinated patients achieved improved CFR28 (odds ratio [OR], 0.19; 95% CI, 0.09 to 0.40), hospitalization (OR, 0.28; 95% CI, 0.11 to 0.69), COVID-19 complications (OR, 0.16; 95% CI, 0.06 to 0.45), and reduced requirement of COVID-19–specific therapy (OR, 0.24; 95% CI, 0.09 to 0.63) and oxygen therapy (OR, 0.24; 95% CI, 0.09 to 0.67) compared with unvaccinated controls. CONCLUSION Our findings highlight a consistent reduction of COVID-19 severity in patients with breast cancer during the Omicron outbreak in Europe. We also demonstrate that even in this population, a complete severe acute respiratory syndrome coronavirus 2 vaccination course is a strong determinant of improved morbidity and mortality from COVID-19.

BACKGROUND. The optimal use of antiresorptive agents (bisphosphonates; denosumab) in patients with bone metastases from solid tumors is uncertain in several aspects, including the initial drug choice and the planned treatment duration, till the long-term therapy. Drug costs, logistics and facilities, patients’ preferences, renal toxicity, and expected risk of Medication-Related Osteonecrosis of the Jaw (MRONJ), as well as other side effects, may conditionate the oncologists’ choice. MATERIAL AND METHODS. Italian oncologists from a study group on bone metastatic disease within the “Rete Oncologica Piemonte-Valle d’Aosta” (a cancer network in North-Western Italy) evaluated scientific literature and current guidelines and recommendations, to answer a PICO (Patient/population; Intervention; Comparison; Outcome) question. The question was: in patients with bone metastases from solid tumors, is treatment with antiresorptive drugs (bisphosphonates or denosumab) amenable to personalized use (for choice of drug and duration of treatment) based on the type of disease, the expected risk of side effects, and patient compliance, as an alternative to “one-fit-for-all” therapy (monthly zoledronic acid or denosumab, indefinitely), in order to: reduce the commitment to the patient and to the oncological structure; reduce economic costs; reduce the risk of medium/long-term side effects (e.g., MRONJ)? RESULTS. The study group analysed the cost of drugs; the engagement of the oncology unit; the patient commitment/compliance; the risk of side effects (renal toxicity, hypocalcaemia, MRONJ); the options of the planned initial duration of treatment; the timing of administration (monthly versus quarterly). Early antiresorptive treatment was recommended (at the diagnosis of bone metastases, after pre-therapy dental evaluation). Four types of tailored treatment options were recommended, in four main different metastatic cancer scenarios. CONCLUSION. A tailored antiresorptive treatment might reduce the number of accesses to oncological structures by the patient, the costs for the structure and for the healthcare system (both in terms of work and cost of drugs), and the risk of medium/long-term side effects (renal failure; MRONJ), potentially without reducing the expected benefits of the treatment.

Supplementary figures 1-5, supplementary tables 1-9

Follicular dendritic cell (FDC) sarcomas are rare mesenchymal tumors with variable clinical, morphologic, and phenotypic characteristics. Transcriptome analysis was performed on multiple FDC sarcomas and compared with other mesenchymal tumors, microdissected Castleman FDCs, and normal fibroblasts. Using unsupervised analysis, FDC sarcomas clustered with microdissected FDCs, distinct from other mesenchymal tumors and fibroblasts. The specific endowment of FDC-related gene expression programs in FDC sarcomas emerged by applying a gene signature of differentially expressed genes (n = 1,289) between microdissected FDCs and fibroblasts. Supervised analysis comparing FDC sarcomas with microdissected FDCs and other mesenchymal tumors identified 370 and 2,927 differentially expressed transcripts, respectively, and on the basis of pathway enrichment analysis ascribed to signal transduction, chromatin organization, and extracellular matrix organization programs. As the transcriptome of FDC sarcomas retained similarity with FDCs, the immune landscape of FDC sarcoma was investigated by applying the CIBERSORT algorithm to FDC sarcomas and non-FDC mesenchymal tumors and demonstrated that FDC sarcomas were enriched in T follicular helper (TFH) and T regulatory (TREG) cell populations, as confirmed in situ by immunohistochemistry. The enrichment in specific T-cell subsets prompted investigating the mRNA expression of the inhibitory immune receptor PD-1 and its ligands PD-L1 and PD-L2, which were found to be significantly upregulated in FDC sarcomas as compared with other mesenchymal tumors, a finding also confirmed in situ. Here, it is demonstrated for the first time the transcriptional relationship of FDC sarcomas with nonmalignant FDCs and their distinction from other mesenchymal tumors.Implications: The current study provides evidence of a peculiar immune microenvironment associated with FDC sarcomas that may have clinical utility. Mol Cancer Res; 15(5); 541–52. ©2017 AACR.

Angioimmunoblastic lymphoma (AILT) is the second most common subtype of peripheral T-cell lymphoma (PTCL) and is characterized by dismal prognosis. Thus far, only a few studies have dealt with its molecular pathogenesis. We performed gene expression profile (GEP) analysis of six AILT, six anaplastic large cell lymphomas (ALCL), 28 PTCL-unspecified (PTCL/U), and 20 samples of normal T lymphocytes (including CD4+, CD8+, and activated and resting subpopulations), aiming to (a) assess the relationship of AILT with other PTCLs, (b) establish the relationship between AILT and normal T-cell subsets, and (c) recognize the cellular programs deregulated in AILT possibly looking for novel potential therapeutic targets. First, we found that AILT and other PTCLs have rather similar GEP, possibly sharing common oncogenic pathways. Second, we found that AILTs are closer to activated CD4+, rather than to resting or CD8+ lymphocytes. Furthermore, we found that the molecular signature of follicular T helper cells was significantly overexpressed in AILT, reinforcing the idea that AILT may arise from such cellular counterpart. Finally, we identified several genes deregulated in AILT, including PDGFRA, REL, and VEGF. The expression of several molecules was then studied by immunohistochemistry on tissue microarrays containing 45 independent AILT cases. Notably, we found that the vascular endothelial growth factor (VEGF) was expressed not only by reactive cells, but also by neoplastic cells, and that nuclear factor-κB (NF-κB) activation is uncommon in AILT, as suggested by frequent exclusively cytoplasmic c-REL localization. Our study provides new relevant information on AILT biology and new candidates for possible therapeutic targets such as PDGFRA (platelet-derived growth factor α) and VEGF. [Cancer Res 2007;67(22):10703–10]

Supplementary File 1 from Gene Expression Analysis of Angioimmunoblastic Lymphoma Indicates Derivation from T Follicular Helper Cells and Vascular Endothelial Growth Factor Deregulation

Supplementary Tables 1-5 from Gene Expression Analysis of Angioimmunoblastic Lymphoma Indicates Derivation from T Follicular Helper Cells and Vascular Endothelial Growth Factor Deregulation

We conducted a retrospective/prospective worldwide study on patients with neuroendocrine neoplasms (NENs) and a molecularly proven SARS-CoV-2 positivity. Preliminary results regarding 85 patients of the INTENSIVE study have been published in 2021. Now we are reporting the 2-year analysis.Here, we are reporting data from consecutive patients enrolled between 1 June 2020, and 31 May 2022. Among the 118 contacted centers, 25 were active to enroll and 19 actively recruiting at the time of data cut-off for a total of 280 patients enrolled. SARS-CoV-2 positivity occurred in 47.5% of patients in 2020, 35.1% in 2021, and 17.4% in 2022. The median age for COVID-19 diagnosis was 60 years. Well-differentiated tumors, non-functioning, metastatic stage, and gastroenteropancreatic (GEP) primary sites represented most of the NENs. COVID-19-related pneumonia occurred in 22.8% of the total, with 61.3% of them requiring hospitalization; 11 patients (3.9%) needed sub-intensive or intensive care unit therapies and 14 patients died (5%), in 11 cases (3.9%) directly related to COVID-19. Diabetes mellitus and age at COVID-19 diagnosis > 70 years were significantly associated with COVID-19 mortality, whereas thoracic primary site with COVID-19 morbidity. A significant decrease in both hospitalization and pneumonia occurred in 2022 vs 2020. In our largest series of NEN patients with COVID-19, the NEN population is similar to the general population of patients with NEN regardless of COVID-19. However, older age, non-GEP primary sites and diabetes mellitus should be carefully considered for increased COVID-19 morbidity and mortality. Relevant information could be derived by integrating our results with NENs patients included in other cancer patients with COVID-19 registries.

Background COVID-19 sequelae can affect about 15% of patients with cancer who survive the acute phase of SARS-CoV-2 infection and can substantially impair their survival and continuity of oncological care. We aimed to investigate whether previous immunisation affects long-term sequelae in the context of evolving variants of concern of SARS-CoV-2. Methods OnCovid is an active registry that includes patients aged 18 years or older from 37 institutions across Belgium, France, Germany, Italy, Spain, and the UK with a laboratory-confirmed diagnosis of COVID-19 and a history of solid or haematological malignancy, either active or in remission, followed up from COVID-19 diagnosis until death. We evaluated the prevalence of COVID-19 sequelae in patients who survived COVID-19 and underwent a formal clinical reassessment, categorising infection according to the date of diagnosis as the omicron (B.1.1.529) phase from Dec 15, 2021, to Jan 31, 2022; the alpha (B.1.1.7)-delta (B.1.617.2) phase from Dec 1, 2020, to Dec 14, 2021; and the pre-vaccination phase from Feb 27 to Nov 30, 2020. The prevalence of overall COVID-19 sequelae was compared according to SARS-CoV-2 immunisation status and in relation to post-COVID-19 survival and resumption of systemic anticancer therapy. This study is registered with ClinicalTrials.gov, NCT04393974. Findings At the follow-up update on June 20, 2022, 1909 eligible patients, evaluated after a median of 39 days (IQR 24-68) from COVID-19 diagnosis, were included (964 [ 50 center dot 7%] of 1902 patients with sex data were female and 938 [49 center dot 3%] were male). Overall, 317 (16 center dot 6%; 95% CI 14 center dot 8-18 center dot 5) of 1909 patients had at least one sequela from COVID-19 at the first oncological reassessment. The prevalence of COVID-19 sequelae was highest in the prevaccination phase (191 [19 center dot 1%; 95% CI 16 center dot 4-22 center dot 0] of 1000 patients). The prevalence was similar in the alpha-delta phase (110 [16 center dot 8%; 13 center dot 8- 20 center dot 3] of 653 patients, p=0 center dot 24), but significantly lower in the omicron phase (16 [6 center dot 2%; 3 center dot 5-10 center dot 2] of 256 patients, p

Background Specific data regarding coronavirus disease 2019 (COVID-19) in patients with neuroendocrine neoplasms (NENs) are lacking. The aim of this study is to describe the characteristics of patients with NENs who tested severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive. Material and methods This is a worldwide study collecting cases of patients with NENs along with a positive nasopharyngeal swab reverse transcriptase-polymerase chain reaction (RT-PCR) test for SARS-CoV-2 between June 1, 2020, and March 31, 2021. Centres treating patients with NENs were directly contacted by the principal investigator. Patients with NENs of any primary site, grade and stage were included, excluding small-cell lung carcinoma and mixed adenoneuroendocrine carcinoma. Results Among 81 centres directly contacted, 88.8% responded and 48.6% of them declined due to lack of cases or interest. On March 31st, 2021, eight recruiting centres enrolled 89 patients. The median age was 64 years at the time of COVID-19 diagnosis. Most patients had metastatic, non-functioning, low-/intermediate-grade gastroenteropancreatic NENs on treatment with somatostatin analogues and radioligand therapy. Most of them had comorbidities. Only 8% of patients had high-grade NENs and 12% were receiving chemotherapy. Most patients had symptoms or signs of COVID-19, mainly fever and cough. Only 3 patients underwent sub-intensive treatment, whereas most of them received medical therapies, mostly antibiotics. In two third of cases, no changes occurred for the anti-NEN therapy. More than 80% of patients completely recovered without sequelae, whereas 7.8% patients died due to COVID-19. Conclusions Patients included in this study reflect the typical NEN population regardless of SARS-CoV-2. In most cases, they overcome COVID-19 without need of intensive care, short-term sequelae and discontinuation of systemic oncological therapy.

BackgroundAs management and prevention strategies against COVID-19 evolve, it is still uncertain whether prior exposure to immune checkpoint inhibitors (ICIs) affects COVID-19 severity in patients with cancer.MethodsIn a joint analysis of ICI recipients from OnCovid (NCT04393974) and European Society for Medical Oncology (ESMO) CoCARE registries, we assessed severity and mortality from SARS-CoV-2 in vaccinated and unvaccinated patients with cancer and explored whether prior immune-related adverse events (irAEs) influenced outcome from COVID-19.FindingsThe study population consisted of 240 patients diagnosed with COVID-19 between January 2020 and February 2022 exposed to ICI within 3 months prior to COVID-19 diagnosis, with a 30-day case fatality rate (CFR30) of 23.6% (95% CI 17.8 to 30.7%). Overall, 42 (17.5%) were fully vaccinated prior to COVID-19 and experienced decreased CFR30(4.8% vs 28.1%, p=0.0009), hospitalization rate (27.5% vs 63.2%, pOverall, 38 patients (15.8%) experienced at least one irAE of any grade at any time prior to COVID-19, at a median time of 3.2 months (range 0.13–48.7) from COVID-19 diagnosis. IrAEs occurred independently of baseline characteristics except for primary tumor (p=0.0373) and were associated with a significantly decreased CFR30(10.8% vs 26.0%, p=0.0462) additionally confirmed by the IPTW-fitted multivariable analysis (aOR 0.47, 95% CI 0.33 to 0.67). Patients who experienced irAEs also presented a higher median absolute lymphocyte count at COVID-19 (1.4 vs 0.8 109 cells/L, p=0.0098).ConclusionAnti-SARS-CoV-2 vaccination reduces morbidity and mortality from COVID-19 in ICI recipients. History of irAEs might identify patients with pre-existing protection from COVID-19, warranting further investigation of adaptive immune determinants of protection from SARS-CoV-2.

Il tumore della mammella è la neoplasia più frequente della donna. Le percentuali di guarigione e sopravvivenza sono molto cresciute negli ultimi anni grazie all’avvento di terapie innovative. La grande importanza sociale che ricopre la malattia ha portato a concentrare sempre di più gli sforzi allo scopo di ottenere i migliori risultati anche mediante alla gestione multidisciplinare della patologia. Viene descritta in questo articolo l’attività del Gruppo Interdisciplinare Cure (GIC) sul tumore della mammella dell’Azienda Ospedaliera di Alessandria.

The differential diagnosis between lymphoplasmacytic lymphoma (LPL) and marginal zone B-cell lymphoma, particularly splenic type (SMZL), can be challenging on onset of bone marrow biopsy (BMB) since morphology and phenotype are not specific and clinical features can overlap or be mildly developed at diagnosis. The LPL-specific L265P mutation in the MYD88 gene is not available in all laboratories, and genetic aberrancies identified in SMZL (del7q, mutations of NOTCH2 and KLF2) are seldom searched in routine practice. The study aim is to investigate the potential role of myeloid nuclear differentiation antigen (MNDA) expression in this specific differential diagnosis. We report MNDA reactivity in 559 patients with small B-cell lymphoma including bone marrow biopsies from 90 LPL and 91 SMZL cases. MYD88 p.Leu265Pro mutation status was assessed and confirmed as positive in 24 of 90 LPL cases, which served as the test set. MNDA staining was negative in 23 of 24 LPL cases in the test set (96%). In the 157 remaining cases (66 LPL, 91 SMZL), which served as the validation set, the MYD88 p.Leu265Pro mutation was unavailable and MNDA was more frequently expressed in SMZL (p 0.00001). In addition, immunohistochemical features more consistent with SMZL (i.e., presence of CD23+ follicular dendritic cell meshworks, polytypic plasma cells, DBA44 reactivity) were more often present in MNDA-positive cases (statistically significant for 2 such parameters). On the widest case series so far published focusing on LPL and SMZL immunohistochemical diagnosis at onset of BMB, we demonstrated that MNDA expression significantly support the diagnosis of SMZL. This observation may be of particular help in cases where the MYD88 p.Leu265Pro mutational status and/or SMZL-related genetic aberrations are unavailable.

Background. Osteonecrosis of the Jaw (ONJ) frequency after antiresorptive treatment in prostate cancer patients largely varied in literature. Patients and Methods. Charts of all prostate cancer patients affected by bone metastases observed at the Oncology Unit of Alessandria Hospital in years 2005-2020 have been reviewed. ONJ frequency after antiresorptive treatment (bisphosphonates and/or denosumab) was investigated in prostate cancer patients with bone metastases undergoing preventive (before start of treatment) and/or screening (during treatment) evaluations, including oral inspection and panoramic dental radiography. Patients received antiresorptive agents according to international guidelines. Results. We examined charts of 120 patients receiving bisphosphonates (mostly zoledronic acid, or pamidronate or ibandronate) or denosumab or sequences of drugs, and evaluated for oral health, 112 being treated since 2006 after pre-treatment oral evaluation. Out of 120 total patients, 8 cases of Osteonecrosis of the Jaw (ONJ) were registered among prostate cancer patients treated at Alessandria Hospital: 2 ONJ cases were detected among 8 patients starting antiresorptive treatment before 2006 and without preventive visit, whereas 6 cases were found among 112 cases receiving dental visit before treatment start (6/112, 5.3%). Furthermore, other 8 ONJ cases in prostate cancer patients were referred by neighbour hospitals to the ONJ multidisciplinary group. Conclusions. Our preliminary data confirm that prostate cancer patients receiving bisphosphonates or denosumab are at not irrelevant risk of ONJ, even if in last decade less intensive schedules of antiresorptive drugs and measures of pre-treatment evaluation were adopted. Further evaluations have been planned to investigate if higher ONJ risk was associated to drug (denosumab versus zoledronic acid), prolonged treatment (> 2 years), pre-existing oral disease (periodontal disease, need for tooth extraction, ill-fitting dentures), and other potential predictive factors.

Background. Osteonecrosis of the Jaw (ONJ) frequency after antiresorptive treatment in prostate cancer patients largely varied in literature. Patients and Methods. Charts of all prostate cancer patients affected by bone metastases observed at the Oncology Unit of Alessandria Hospital in years 2005-2020 have been reviewed. ONJ frequency after antiresorptive treatment (bisphosphonates and/or denosumab) was investigated in prostate cancer patients with bone metastases undergoing preventive (before start of treatment) and/or screening (during treatment) evaluations, including oral inspection and panoramic dental radiography. Patients received antiresorptive agents according to international guidelines. Results. We examined charts of 120 patients receiving bisphosphonates (mostly zoledronic acid, or pamidronate or ibandronate) or denosumab or sequences of drugs, and evaluated for oral health, 112 being treated since 2006 after pre-treatment oral evaluation. Out of 120 total patients, 8 cases of Osteonecrosis of the Jaw (ONJ) were registered among prostate cancer patients treated at Alessandria Hospital: 2 ONJ cases were detected among 8 patients starting antiresorptive treatment before 2006 and without preventive visit, whereas 6 cases were found among 112 cases receiving dental visit before treatment start (6/112, 5.3%). Furthermore, other 8 ONJ cases in prostate cancer patients were referred by neighbour hospitals to the ONJ multidisciplinary group. Conclusions. Our preliminary data confirm that prostate cancer patients receiving bisphosphonates or denosumab are at not irrelevant risk of ONJ, even if in last decade less intensive schedules of antiresorptive drugs and measures of pre-treatment evaluation were adopted. Further evaluations have been planned to investigate if higher ONJ risk was associated to drug (denosumab versus zoledronic acid), prolonged treatment (> 2 years), pre-existing oral disease (periodontal disease, need for tooth extraction, ill-fitting dentures), and other potential predictive factors.

PATIENTS AT RISK OF OSTEONECROSIS OF THE JAW (ONJ) INCLUDE MOSTLY CANCER AND MYELOMA PATIENTS RECEIVING ANTIRESORPTIVE TREATMENTS (BISPHOSPHONATES AND DENOSUMAB) WITH/WITHOUT BIOLOGICAL AGENTS, BUT ALSO PATIENTS WITH OSTEOPOROSIS AND RHEUMATOLOGIC DISORDERS. ONJ CASES WERE FIRSTLY DIAGNOSED IN OUR HOSPITAL ON 2005. SINCE 2006, A ONJ MULTIDISCIPLINARY TEAM WAS ESTABLISHED (INCLUDING MAXILLOFACIAL SURGEONS / DENTISTS, ONCOLOGISTS, HEMATOLOGISTS, NURSES, RADIOLOGISTS, NUCLEAR MEDICINE AND OTHER MEDICINE SPECIALISTS, DATA MANAGERS). PREVENTIVE (RISK REDUCTION) MEASURES BEFORE ANTIRESORPTIVE TREATMENT (DENTAL VISIT, DENTAL PANORAMIC RX, EVENTUAL TEETH EXTRACTIONS, DENTAL AND DENTURE CARE) HAVE BEEN PLANNED, ACCORDING TO EARLY RECOMMENDATIONS AND THEIR MODIFICATIONS. FURTHERMORE IN THE OSTEONECROSIS PREVENTION AND SCREENING OFFICE OTHER PATIENTS RECEIVED CARE IF : A) ONJ WAS SUSPECTED AFTER TREATMENT FOR CANCER AND MYELOMA IN NEIGHBORING HOSPITALS, OR B) ONJ WAS SUSPECTED AMONG OSTEOPOROSIS PATIENTS IN THE TERRITORY BY PRIVATE PRACTICE DENTISTS. MORE THAN 900 PATIENTS WERE VISITED AND REGISTERED IN 2006-2020 YEARS. CASES OF SUSPECTED ONJ WERE 127 (45 MALE, 82 FEMALE). TWENTY-FOUR CASES WERE EXCLUDED BY ANALYSIS DUE TO UNCONFIRMED DIAGNOSIS OR INSUFFICIENT DATA. CHARACTERISTICS OF 103 CASES OF ONJ CONFIRMED ACCORDING TO ITALIAN (SIPMO-SICMF) DEFINITION AND RECOMMENDATIONS WERE REVIEWED. DISEASE: 40 BREAST CANCER; 16 PROSTATE CANCER; 11 MYELOMA; 7 RENAL CELL CANCER; 4 LUNG CANCER; 7 OTHER CANCERS; 18 OSTEOPOROSIS AND OTHER NON MALIGNANT DISORDERS. DISTRIBUTION OF DRUGS ASSOCIATED TO ONJ (ZOLEDRONIC ACID, DENOSUMAB, PAMIDRONATE, ALENDRONATE, RISEDRONATE, IBANDRONATE, CLODRONATE, BEVACIZUMAB, SUNITINIB) CHANGED ALONG YEARS.

Survival of cancer and myeloma patients after diagnosis of bone lesions is largely variable. Appropriate medical therapy together with antiresorptive treatment (bisphosphonates or denosumab) can obtain prolonged survival with adequate quality of life. Osteonecrosis of Jaws (ONJ) is not rare in patients with bone metastatic cancer and myeloma patients, occurring mostly after prolonged antiresorptive treatment. Expected survival can influence the choice of antiresorptive treatment, the perception of ONJ risk, and even the ONJ management. We reviewed survival data after start of antiresorptive treatment of 509 ONJ patients registered in a cancer network database (Rete Oncologica Piemonte-Valle d’Aosta, North-Western Italy). Main characteristics: 196 males, 313 females; median age: 68 (39-89) years. Underlying disease: breast cancer: 42.9%; myeloma: 25.3%; prostate cancer: 17.2%; lung cancer: 6.7%; renal cancer: 2.5%; other cancer types: 4.3%. Main antiresorptive treatment: zoledronic acid: 79.4%; denosumab: 5.3%; other drugs/sequences: 15.3%. Actuarial median survival (range) after the start of antiresorptive treatment was 66.0 (95% CI 57-77) months for breast cancer patients, 77.3 (95% CI 61.9-86.8) months for myeloma patients, 47.3. (95% CI 37.8-51.9) months for prostate cancer patients, 29.4 (95% CI 20.4-40.1) months for lung cancer patients, 39.4 (95% CI 20-107.3) months for renal cancer patients, 82.4 (95% CI 51.9-150.9) months for other cancer patients. Two-, three- and four-year actuarial survival rates were respectively 91.7%%, 80.2%, 67.4% for breast cancer patients, 91.4%, 83.7%, 68.9% for myeloma patients, 78.4%, 61.2%, 41.9% for prostate cancer patients; 55.8%, 32.3%, 23.5% for lung cancer patients; 61.5%, 53.8%, 46.1% for renal cancer patients; 81.8%, 77.3%, 68.1% for others cancer types. Our data support careful evaluation of short and long-term actuarial ONJ risk (versus short-term absolute risk) in the choice of antiresorptive treatment duration for bone metastatic cancer and myeloma patients. Furthermore, exclusion of jawbone surgery due to expected short survival in most of ONJ patients seems not warranted.

Objectives: To analyse the organisational changes adopted by the Oncology SC during the Covid-19 emergency in order to identify their future applicability as an ordinary model of oncology patient management. Methodology: Application of ministerial recommendations, of the Piedmont and Aosta Valley Oncology Network and of the main scientific societies on the management of oncological patients during the pandemic and in phase 2. Results: During the pandemic, organisational models and pathways were adopted that ensured continuity of care and patient safety and can also be applied in the post-Covid phase. Conclusions: The reorganisation model of Oncology during the Covid-19 emergency was effective and some of the pathways adopted may constitute an ordinary tool of activity.

Purpose: Hospital admission is a frequent occurrence among patients with cancer, and a significant proportion of patients admitted to medical units have cancer. Their hospital stay has features that may be different compared with patients without cancer. We performed a retrospective analysis of the characteristics of patients with cancer admitted for medical conditions. Patients and methods: We studied the administrative data of patients with solid cancer admitted to the medical department of a large referral hospital over a 12-month period and compared them with those of patients without cancer. Results: Seven thousand eight hundred two consecutive admissions were analysed, of which 1099 (14.1%) had a principal or associated diagnosis of cancer. Admissions were distributed across 12 units, with 44% concentrated in the medical oncology unit and 56% in other units. Patients with cancer were more frequently men and were younger than patients without cancer. Admission less frequently involved the emergency department (ED), while discharge was more frequently assisted. The in-hospital death rate was higher, as was the readmission rate. Length of stay was longer (11.3 days vs. 9.8 days; p < 0.0001). Patients with cancer admitted to the medical oncology unit used the ED even less, and their length of stay was shorter than that of patients with cancer admitted in other units. Conclusions: The in-hospital pathway of patients with cancer displays specific issues and adds complexity to hospital stay of patients with medical conditions. The medical oncology unit plays a role in reducing ED use and in providing efficient care. The evidence gathered should help in shaping new models of care and in improving adequate clinical competencies. (C) 2020 Elsevier Ltd. All rights reserved.

Background The optimal timing of surgery in relation to chemoradiation is still controversial. Retrospective analysis has demonstrated in the recent decades that the regression of adenocarcinoma can be slow and not complete until after several months. More recently, increasing pathologic Complete Response rates have been demonstrated to be correlated with longer time interval. The purpose of the trial is to demonstrate if delayed timing of surgery after neoadjuvant chemoradiotherapy actually affects pathologic Complete Response and reflects on disease-free survival and overall survival rather than standard timing. Methods The trial is a multicenter, prospective, randomized controlled, unblinded, parallel-group trial comparing standard and delayed surgery after neoadjuvant chemoradiotherapy for the curative treatment of rectal cancer. Three-hundred and forty patients will be randomized on an equal basis to either robotic-assisted/standard laparoscopic rectal cancer surgery after 8 weeks or robotic-assisted/standard laparoscopic rectal cancer surgery after 12 weeks. Discussion To date, it is well-know that pathologic Complete Response is associated with excellent prognosis and an overall survival of 90%. In the Lyon trial the rate of pCR or near pathologic Complete Response increased from 10.3 to 26% and in retrospective studies the increase rate was about 23–30%. These results may be explained on the relationship between radiation therapy and tumor regression: DNA damage occurs during irradiation, but cellular lysis occurs within the next weeks. Study results, whether confirmed that performing surgery after 12 weeks from neoadjuvant treatment is advantageous from a technical and oncological point of view, may change the current pathway of the treatment in those patient suffering from rectal cancer. Trial registration ClinicalTrials.gov NCT3465982.

Blastic Plasmacytoid Dendritic Cell Neoplasm is a rare and aggressive hematological malignancy currently lacking an effective therapy. To possibly identify genetic alterations useful for a new treatment design, we analyzed by whole-exome sequencing fourteen Blastic Plasmacytoid Dendritic Cell Neoplasm patients and the patient-derived CAL-1 cell line. The functional enrichment analysis of mutational data reported the epigenetic regulatory program as the most significantly undermined (P

We read the letter from Dr. Fusco and colleagues with great interest, and we would like to thank them for the stimulating comments regarding our paper "Medication-Related Osteonecrosis of the Jaws and CDK4/6 Inhibitors: A Recent Association" [...].

e16205 Background: Data about neuroendocrine neoplasms (NENs) patients with SARS-CoV-2 are scanty and specific indications for clinical practice are missing. Our aim is to create an international registry about NENs patients affected by SARS-CoV-2 positivity to give a worldwide representation of the situation. Methods: This is an observational retrospective/prospective multicenter survey based on a direct email invitation. All types of NEN are eligible except SCLC and MiNEN. Patients fulfilling the inclusion criteria from March 1st, 2020 up to the end pf pandemic will be recruited. Electronic CRFs are filled out using the REDCap database. Local Institutional Review Board approval is required before data entry. Results: Eighty-one centers, 24 in and 57 outside Italy, representing 39 countries and 5 continents, were contacted. Fourteen centers did not respond and 15 declined the invitation. Among the remaining 52, 6 centers are currently recruiting and 8 are active but not recruiting yet. As of the current abstract submission deadline, 67 patients have been included, mostly GEP-NET (75%), non-functioning (86%), metastatic (85%) and on active treatment [47% somatostatin analogs (SSAs), 10% everolimus, 12% tirosin-kinase inhibitors (TKIs), 10% peptide receptor radionuclide therapy (PRRT), 15% chemotherapy]. Median age at NEN diagnosis was 57 years whilst the median age at SARS-CoV-2 diagnosis was 62 years. Almost all patients reported COVID-19-related symptoms, more commonly fever (67% of patients), cough (55%) and dyspnea (51%), in 28% of cases exertional and in 22% at rest. More than one third of patients (n, 24) had a pneumonia. The most common therapies for COVID-19 were antibiotics, steroids and hydroxychloroquine. Eleven patients (16%) needed oxygen therapy, three (4%) sub-intensive care and none intensive care. Fifty-six patients (84%) clinically recovered, six (9%) with sequelae, whereas five (7%) died. Among these latter 4 had a NET and 1 a NEC, and no patients have been receiving chemotherapy. With regard to the anti-tumor therapy no change occurred in 66% of patients, temporary interruption in 30%, and definitive discontinuation in 3%, 2% missing. Conclusions: Most of the NEN patients completely recovered from COVID-19, in many cases without any anti-tumor therapy adjustment. No clear correlations were observed with type, primary site and treatment of NEN. The recruitment is ongoing.

Follicular dendritic cell (FDC) sarcomas are rare mesenchymal tumors with variable clinical, morphologic, and phenotypic characteristics. Transcriptome analysis was performed on multiple FDC sarcomas and compared with other mesenchymal tumors, microdissected Castleman FDCs, and normal fibroblasts. Using unsupervised analysis, FDC sarcomas clustered with microdissected FDCs, distinct from other mesenchymal tumors and fibroblasts. The specific endowment of FDC-related gene expression programs in FDC sarcomas emerged by applying a gene signature of differentially expressed genes (n = 1,289) between microdissected FDCs and fibroblasts. Supervised analysis comparing FDC sarcomas with microdissected FDCs and other mesenchymal tumors identified 370 and 2,927 differentially expressed transcripts, respectively, and on the basis of pathway enrichment analysis ascribed to signal transduction, chromatin organization, and extracellular matrix organization programs. As the transcriptome of FDC sarcomas retained similarity with FDCs, the immune landscape of FDC sarcoma was investigated by applying the CIBERSORT algorithm to FDC sarcomas and non-FDC mesenchymal tumors and demonstrated that FDC sarcomas were enriched in T follicular helper (TFH) and T regulatory (TREG) cell populations, as confirmed in situ by immunohistochemistry. The enrichment in specific T-cell subsets prompted investigating the mRNA expression of the inhibitory immune receptor PD-1 and its ligands PD-L1 and PD-L2, which were found to be significantly upregulated in FDC sarcomas as compared with other mesenchymal tumors, a finding also confirmed in situ. Here, it is demonstrated for the first time the transcriptional relationship of FDC sarcomas with nonmalignant FDCs and their distinction from other mesenchymal tumors. Implications: The current study provides evidence of a peculiar immune microenvironment associated with FDC sarcomas that may have clinical utility. Mol Cancer Res; 15(5); 541–52. ©2017 AACR.

Los girasoles ciegos de Alberto Mendez es una coleccion de cuatro cuentos publicada en el ano 2004 en el contexto de la entonces recien revitalizada ‘narrativa de la memoria’, dentro del marco de la literatura espanola ultracontemporanea. Objetivo de este trabajo es la formulacion de un analisis pormenorizado de algunos aspectos que vinculan el contenido de las historias narradas con las caracteristicas tecnicas del genero elegido, con el fin de descifrar la declinacion del cuento llevada a cabo por Mendez y su aportacion en el debate trans-literario sobre el recuerdo compartido del trauma de la guerra civil y el franquismo. Finalidad ultima de la argumentacion aqui expuesta es comentar el concepto de ‘derrota universal’ propuesto por el autor, de sus distintas modulaciones dentro del texto y de las modalidades de configuracion de un duelo inclusivo que pacifique, por fin, la memoria heredada de un bache historico tan reciente como controvertido.

This essay is a synchronic exploration of peninsular literature in Spanish, and its main aim is to draw a map – within the inescapable boundaries imposed by strict immediacy – of tendencies, developments, filiations, thematic patterns and socio-political contaminations that may characterise it. Starting from a negotiated definition of ‘the aughts’ as a referential frame for this reflection, the argumentation translates into an analysis of ultra-contemporary Spanish novel as a mutant and polymorphous phenomenon, on the edge (or past it, according to those who claim it has already died) of the expiration ofnovela social, the acrobatic statements ofafterpop, the intra- and extra-literary claims of postmemory, the permeability towards the worldwide diffusion of brevity and auto-fiction, the conflict between local hyper-specificity and panhispanic pangea., Rassegna iberistica