The Impact of COVID-19 on Treatment Practices for Patients With Early Breast Cancer: A Cross-Sectional Study From a Large Cancer Center in Italy.

INTRODUCTION: The Coronavirus Disease 2019 (COVID-19) has disrupted health services worldwide. The evidence on the impact of the pandemic on cancer care provision, however, is conflicting. We aimed to audit the management of patients diagnosed with early breast cancer (EBC) during the pandemic in a large, tertiary-level cancer center in Italy. METHODS: We conducted a cross-sectional study to track the route to first treatment for patients diagnosed with EBC during 2019, 2020, and 2021. We abstracted data for all consecutive patients referred to the Veneto Institute of Oncology (Padua, Italy). We defined as point of contact (POC) the date of the first consultation with a breast cancer specialist of the breast unit. First treatment was defined as either upfront surgery or neoadjuvant chemotherapy (NACT). RESULTS: We reviewed medical records for 878 patients for whom an MDT report during 2019-2021 (April through June) was available. Of these, 431 (49%) were eligible. The proportion of screen-detected tumors was larger in 2019 and 2021 than in 2020 (59%). Conversely, the proportion of screen-detected tumors was offset by the proportion of palpable tumors in 2020 (P = .004). Distribution of tumor and nodal stage was unchanged over time, but in situ tumors were slightly fewer in 2020 than in 2019 or 2021. The adjusted odds ratio for treatment delay (45 days or more) was 0.87 for 2020 versus 2019 (95% CI, 0.5-1.53) and 0.9 for 2021 versus 2019 (95% CI, 0.52-1.55). CONCLUSIONS: There was no evidence for major changes in the management of patients with EBC during 2019-2021 and no treatment delays were observed. Our findings suggest that more women presented with palpable nodules at diagnosis, but the stage distribution did not change over time. Validation on a larger cohort of patients is warranted to robustly assess the impact of the COVID-19 pandemic on treatment practices for patients with EBC.

Use of scalp cooling device to prevent alopecia for early breast cancer patients receiving chemotherapy: A prospective study.

Chemotherapy-induced alopecia (CIA) affects the majority of patients receiving chemotherapy (CT) for early breast cancer. It is a highly distressing side effect of CT, with psychological and social impact. Primary aim of the present analysis was to assess the efficacy of scalp cooling with DigniCap® in preventing CIA. Success rate was defined as patients' self-reported hair loss <50% according to Dean scale. In this analysis, we reported success rate at 3 weeks after the first CT course and at 3 weeks after the last CT course. Secondary endpoints included self-reported tolerability and patients' judgment on scalp cooling performance. Consecutive early breast cancer patients admitted to Istituto Oncologico Veneto who were recommended to receive neoadjuvant or adjuvant CT, were eligible to undergo scalp cooling during the CT administration within this study. 135 patients were included: 74% received adjuvant CT and 26% neoadjuvant CT (P < .001). The type of CT was: docetaxel-cyclophosphamide (26%), paclitaxel (23%), epirubicin-cyclophosphamide followed by paclitaxel (32%), and paclitaxel followed by epirubicincyclophosphamide (19%). The rate of success in preventing alopecia was 77% (104/135) at 3 weeks from the start of CT and 60% (81/135) at 3 weeks from the end of treatment. Higher success rates were reported in non-anthracycline (71%) compared to anthracycline-containing CT regimens (54%; P < 0.001). Premature discontinuation of scalp cooling was reported in 29/135 patients (21.5%), including withdrawal for alopecia (16/29), for low scalp cooling tolerability (8/29) or both (5/29). Scalp cooling was generally well tolerated. These results overall suggest that the use of scalp cooling is effective in preventing alopecia in the majority of early breast cancer patients receiving neoadjuvant or adjuvant CT, especially for patients undergoing a taxane-based non-anthracycline regimen.

Beyond breast specific-Graded Prognostic Assessment in patients with brain metastases from breast cancer: treatment impact on outcome.

Brain metastases are a serious relatively common complication of breast cancer. We evaluated prognostic factors for survival after diagnosis of brain metastases from breast cancer in a contemporary cohort of patients. Patients diagnosed with breast cancer brain metastases at our institution between 1999 and March 2016 were evaluated. Overall survival was defined as time from brain metastasis diagnosis to death or last follow-up. Patients were classified according to the Breast cancer-specific Graded Prognostic Assessment (BS-GPA), based on age, Karnofsky performance score and breast cancer phenotype. 181 patients were identified. Tumor phenotype distribution was as follows: triple negative (TN, 18.8%), hormone receptor (HR)-HER2+ (16.6%), HR+HER2+ (23.2%) and HR+HER2- (30.9%), not available (10.5%). Median overall survival from brain metastasis diagnosis was 7.7 mos (95% CI 5.4-10.0 mos). Although TN patients experienced the worse outcome, no significant difference was observed across tumor phenotypes (median 5.1, 7.7, 11.0 and 8.6 months in TN, HR-HER2+, HR+HER2+, HR+HER2-, p = 0.081). The BS-GPA index was significantly associated with overall survival (median 18.8, 8.8, 6.2 and 3.6 months, respectively, for BS-GPA categories 3.5-4, 2.5-3, 1.5-2 and 0-1, p = 0.014). Increased number of local treatments for brain metastasis (radiotherapy or neurosurgery) or the administration of systemic therapy after brain metastasis diagnosis were also significant predictors of better overall survival (p < 0.001) and, when evaluated in multivariate analysis with BS-GPA, both added independent prognostication beyond BS-GPA. Patient-related features, tumor phenotype and multimodal treatments all independently contribute to modulate prognosis of patients diagnosed with breast cancer brain metastases.

Leave no one behind: A global survey of the current state of geriatric oncology practice by SIOG national representatives.

INTRODUCTION: The Sustainable Development Goals of the United Nations include a commitment to "leave no one behind" as a universal goal. To achieve this in geriatric oncology (GO) worldwide, it is important to understand the current state of GO at an international level. The International Society of Geriatric Oncology (SIOG) has several National Representatives (NRs) who act as SIOG's delegates in their respective countries. The NRs took part in this international survey exploring the state of GO practice, identifying barriers and solutions. MATERIALS AND METHODS: The NRs answered open-ended questions by email from February 2020 to October 2022. The questionnaire domains included the demographic information of older adults for their countries, and the NRs' opinions on whether GO is developing, what the barriers are to developing GO, and proposed actions to remove these barriers. The demographic data of each country reported in the survey was adjusted using literature and database searches. RESULTS: Twenty-one of thirty countries with NRs (70%) participated in this questionnaire study: 12 European, four Asian, two North American, two South American, and one Oceanian. The proportion of the population aged ≥75 years varied from 2.2% to 15.8%, and the average life expectancy also varied from 70 years to 86 years. All NRs reported that GO was developing in their country; four NRs (18%) reported that GO was well developed. Although all NRs agreed that geriatric assessment was useful, only three reported that it was used day-to-day in their countries' clinical practice (14%). The major barriers identified were the lack of (i) evidence to support GO use, (ii) awareness and interest in GO, and (iii) resources (time, manpower, and funding). The major proposed actions were to (i) provide new evidence through clinical trials specific for GO patients, (ii) stimulate awareness through networking, and (iii) deliver educational materials and information to healthcare providers and medical students. DISCUSSION: This current survey has identified the barriers to GO and proposed actions that could remove them. Broader awareness seems to be essential to implementing GO. Additional actions are needed to develop GO within countries and can be supported through international partnerships.

Oxaliplatin prior to PARP inhibitor in BRCA-mutated ovarian cancer.

Background: The use of PARP inhibitor (PARPi) has shown a considerable benefit in progression-free survival (PFS) in relapsed, platinum-sensitive epithelial ovarian cancer (OC). Objective: Our study aimed to investigate the impact of the last platinum-based chemotherapy treatment in response to PARPi. Design: Retrospective cohort study. Patients and methods: The study involved 96 consecutive, pretreated, platinum-sensitive advanced OC patients. Demographics and clinical data were retrieved from clinical records. PFS and overall survival (OS) were calculated from the start of PARPi. Results: Germline BRCA mutation was investigated in all cases. Platinum-based chemotherapy before PARPi maintenance therapy included pegylated liposomal doxorubicin-oxaliplatin (PLD-Ox) in 46 patients (48%) and other platinum-based chemotherapy in 50 patients (52%). During a median follow-up of 22 months from the beginning of PARPi therapy, 57 patients relapsed (median PFS: 12 months) and 64 patients died (median OS: 23 months). During multivariable analysis, receiving PLD-Ox before PARPi was associated with improved PFS [hazard ratio (HR): 0.46, 95% CI: 0.26-0.82] and OS (HR: 0.48, 95% CI: 0.27-0.83). In 36 BRCA-mutated patients, PLD-Ox was associated with improved PFS (2-year PFS: 70.0% versus 25.0%, p = 0.02). Conclusion: Receiving PLD-Ox before PARPi may improve prognosis in platinum-sensitive advanced OC patients and may provide advantages in the BRCA-mutated subgroup.

The activity and safety of electrochemotherapy in persistent chest wall recurrence from breast cancer after mastectomy: a phase-II study.

Electrochemotherapy (ECT) represents an attractive locoregional therapy for unresectable chest wall recurrence (CWR) from breast cancer. Thirty-five patients with cutaneous CWR after mastectomy who experienced progression despite re-irradiation and extensive systemic treatments were administered bleomycin-based ECT. Local response, toxicity, and superficial control were evaluated. Out of 516 metastases (median 15/patient, range 1-50), response was assessed on 196 target lesions (median size 20 mm, range 10-220). Patients received a median of 2 ECT courses (range 1-3). Two-month objective response was as follows: 54.3 % complete (19/35 patients), 37.1 % partial (13/35), and 8.6 % no change (3/35). Twenty-three patients (65.7 %) developed new lesions (NL) after a median time of 6.6 months (range 2.3-29.5), therefore 1, 2, or 3 ECT cycles were required in 14, 15, and 6 patients, respectively. Median follow-up was 32 months (range 6-53) and the 3-year local control rate was 81 %. Related morbidity was mild, increased after retreatments and consisted primarily of pain (reported as "moderate"/"severe" by 6, 13, and 17 % of patients 1 month after the first, second, and third application, respectively) and dermatological toxicity (acute G3 skin ulceration in 14, 20, and 33 % of patients, respectively). Less than 10 metastases (P < 0.001), the narrower area of tumor spread on the chest wall (P = 0.022), complete response achievement (P = 0.019), and post-ECT endocrine instead of chemotherapy (P = 0.025) were associated to NL-free survival. Only fewer skin metastases, hazard ratio (HR) 0.122, 95 % confidence interval (CI) 0.037-0.397, P < 0.001, and contained superficial spread, HR 0.234, 95 % CI 0.067-0.818, P = 0.023, were predictors for longer NL-free survival. ECT showed a satisfactory activity in refractory breast cancer CWR, providing sustained local control. Patients with fewer and less scattered skin metastases are less likely to develop NL. Partial responders and NL can be handled with additional ECT albeit increasing local pain and skin toxicity.

Preventive effect of risedronate on bone loss and frailty fractures in elderly women treated with anastrozole for early breast cancer.

The aim of this study was to assess the effect of adjuvant anastrozole, alone or associated with risedronate, on BMD and bone fracture risk in women more than 70 years old with hormone receptor-positive early breast cancer (EBC). In a group of 51 elderly women (aged 76.4 ± 5.0 years) considered for adjuvant aromatase inhibitors for EBC, 24 patients with T-scores ≥ -2 and no prevalent fractures received anastrozole 1 mg/day (group A), and 27 patients with T-scores < -2, or with T-scores ≥ -2 and prevalent fractures (group B), received anastrozole (1 mg/day) plus risedronate (35 mg/week). Both groups received supplementation with 1 g calcium carbonate and 800 IU vitamin D per day. Differences in BMD and frailty fractures were evaluated after 1 and 2 years. In group A, significant decreases in BMD were observed in the lumbar spine (Δ BMD, -0.030 ± 0.04 g/cm², P < 0.05), femoral neck (Δ BMD, -0.029 ± 0.05 g/cm², P < 0.05), and trochanter (Δ BMD, -0.026 ± 0.03 g/cm², P < 0.01) after 2 years. The greatest percent reduction in height (Hpr) emerged in the thoracic spine (3.6 ± 2.4%, P < 0.01), although only one incident vertebral fracture was observed. In group B, BMD increased in the lumbar spine (Δ BMD, 0.038 ± 0.04, P < 0.001), although no significant changes were seen in the hip regions. The decline in Hpr was negligible (about 1%). No incident fractures were observed at follow-up. In conclusion, anastrozole treatment for EBC in elderly women seems to have only mild negative effects on the femoral bone. Risedronate makes the use of anastrozole safer, even for osteopenic or osteoporotic elderly patients.

Corrigendum: Results of the ECHO (Eating habits CHanges in Oncologic patients) Survey: An Italian Cross-Sectional Multicentric Study to Explore Dietary Changes and Dietary Supplement Use, in Breast Cancer Survivors.

[This corrects the article DOI: 10.3389/fonc.2021.705927.].

ESR1 Gene Mutation in Hormone Receptor-Positive HER2-Negative Metastatic Breast Cancer Patients: Concordance Between Tumor Tissue and Circulating Tumor DNA Analysis.

Endocrine therapy represents the cornerstone of treatment in hormone receptor-positive (HR+), HER2-negative metastatic breast cancer (mBC). The natural course of this disease is marked by endocrine resistance, mainly due to Estrogen Receptor 1 (ESR1) acquired mutations. The aim of this study is to evaluate the concordance between ESR1 status in metastatic tumor specimens and matched circulating tumor DNA (ctDNA). Forty-three patients with HR+, HER2-negative mBC underwent both a metastatic tumor biopsy and a liquid biopsy at the time of disease progression. DNA extracted from formalin fixed paraffin embedded (FFPE) tumor specimens and ctDNA from matched plasma were analyzed by droplet digital (dd)PCR for the main ESR1 mutations (Y537S, Y537C, Y537N, D538G, E380Q). We observed a total mutation rate of 21%. We found six mutations on tissue biopsy: Y537S (1), D538G (2), Y537N (1), E380Q (2). Three patients with no mutations in tumor tissue had mutations detected in ctDNA. The total concordance rate between ESR1 status on tumor tissue and plasma was 91%. Our results confirm the potential role of liquid biopsy as a non-invasive alternative to tissue biopsy for ESR1 mutation assessment in mBC patients.

Results of the ECHO (Eating habits CHanges in Oncologic patients) Survey: An Italian Cross-Sectional Multicentric Study to Explore Dietary Changes and Dietary Supplement Use, in Breast Cancer Survivors.

The role of a healthy diet in cancer prevention is well recognized. Recent data indicate that following the same advices can also improve cancer survivors' quality of life. Breast cancer (BC) patients are commonly concerned about diet and nutrition and frequently express the need to obtain health-related information and the will to change their diet and lifestyle. Hence, be aware of survivors' dietary changes and information needs is crucial for healthcare professionals to guide them toward optimal lifestyle choices. In order to investigate eating habits changes in a BC survivors' population, we conceived the cross-sectional multicentric study ECHO (Eating habits CHanges in Oncologic patients) Survey. Data were collected from 684 patients, diagnosed with invasive breast cancer, in order to investigate their changes in food consumption, use of supplements, or the beginning of a specific diet, after BC diagnosis. We also examined the sources of information used and if any modification in their diets was reported to the oncologist. We primarily observed that patients increased their consumption of vegetables, pulses, nuts, fruits, wholemeal bread/pasta, grains and fish; while decreasing red and processed meat, refined bread/pasta, baked good and animal fat consumption. Survivors also reported the use of dietary supplements, mainly vitamins, aimed at counteracting therapies' side effects. Changes in nutritional habits were often adopted without asking or informing the oncologist. Despite BC survivors made some positive changes in their nutritional habits, those modifications were mostly pursued by less than half of them, while the majority of patients consumed nutritional supplements after diagnosis. These results, as well as the failure to communicate with the physicians, reinforce the need to both improve the patient-healthcare professional relationship and to develop tailored nutrition counselling and intervention programs for cancer survivors.

Predicting steady-state endoxifen plasma concentrations in breast cancer patients by CYP2D6 genotyping or phenotyping. Which approach is more reliable?

In previous studies, steady-state Z-endoxifen plasma concentrations (ENDOss) correlated with relapse-free survival in women on tamoxifen (TAM) treatment for breast cancer. ENDOss also correlated significantly with CYP2D6 genotype (activity score) and CYP2D6 phenotype (dextromethorphan test). Our aim was to ascertain which method for assessing CYP2D6 activity is more reliable in predicting ENDOss. The study concerned 203 Caucasian women on tamoxifen-adjuvant therapy (20 mg q.d.). Before starting treatment, CYP2D6 was genotyped (and activity scores computed), and the urinary log(dextromethorphan/dextrorphan) ratio [log(DM/DX)] was calculated after 15 mg of oral dextromethorphan. Plasma concentrations of TAM, N-desmethyl-tamoxifen (ND-TAM), Z-4OH-tamoxifen (4OH-TAM) and ENDO were assayed 1, 4, and 8 months after first administering TAM. Multivariable regression analysis was used to identify the clinical and laboratory variables predicting log-transformed ENDOss (log-ENDOss). Genotype-derived CYP2D6 phenotypes (PM, IM, NM, EM) and log(DM/DX) correlated independently with log-ENDOss. Genotype-phenotype concordance was almost complete only for poor metabolizers, whereas it emerged that 34% of intermediate, normal, and ultrarapid metabolizers were classified differently based on log(DM/DX). Multivariable regression analysis selected log(DM/DX) as the best predictor, with patients' age, weak inhibitor use, and CYP2D6 phenotype decreasingly important: log-ENDOss = 0.162 - log(DM/DX) × 0.170 + age × 0.0063 - weak inhibitor use × 0.250 + IM × 0.105 + (NM + UM) × 0.210; (R2  = 0.51). In conclusion, log(DM/DX) seems superior to genotype-derived CYP2D6 phenotype in predicting ENDOss.

Prognostic factors in phyllodes tumours of the breast: retrospective study on 166 consecutive cases.

BACKGROUND: Phyllodes tumours (PTs) are rare fibroepithelial tumours accounting for <1% of all breast tumours. We assessed clinicopathological features and their prognostic effect in a single-institution patients' cohort. METHODS: Patients diagnosed with PT between 2001 and 2018 at our institution were identified. Clinical, surgical and pathological features were collected. Phyllodes-related relapse was defined as locoregional or distant recurrence (contralateral excluded), whichever first. RESULTS: A total of 166 patients were included: 115 with benign, 30 with borderline and 21 with malignant PTs. Features associated with malignant PT were younger age, larger T size, higher mitotic count, marked cytological atypia, stromal overgrowth, stromal hypercellularity, necrosis and heterologous differentiation (all p<0.01). The majority of patients with malignant PT underwent mastectomy (63.2% vs 3% of benign/borderline, p<0.001) and had negative surgical margins (83.3%). 4-year cumulative phyllodes-related relapse incidence was 7% for benign/borderline PT and 21.3% for malignant PT (p=0.107). In the entire cohort, marked cellular atypia and heterologous differentiation were associated with worse phyllodes-related relapse-free survival (HR 14.10, p=0.036 for marked vs mild atypia; HR 4.21, p=0.031 for heterologous differentiation present vs absent). For patients with benign PT, larger tumour size was associated with worse phyllodes-related relapse-free survival (HR 9.67, p=0.013 for T>5 cm vs T≤2 cm). Higher tumour-infiltrating lymphocytes (TILs) were associated with borderline and malignant PT (p=0.023); TILs were not associated with phyllodes-related relapse-free survival (HR 0.58, p=0.361 for TILs>2% vs≤2%). Overall, four patients died because of PT: three patients with malignant and one with borderline PT. CONCLUSIONS: Patients with malignant PT had increased rates of phyllodes-related relapse and phyllodes-related death. Cellular atypia and heterologous differentiation were poor prognostic factors in the entire cohort; large tumour size was associated with an increased risk of phyllodes-related relapse in benign PT.

Circulating biomarkers and cardiac function over 3 years after chemotherapy with anthracyclines: the ICOS-ONE trial.

AIMS: A multicentre trial, ICOS-ONE, showed increases above the upper limit of normality of cardiac troponin (cTn) in 27% of patients within 12 months after the end of cancer chemotherapy (CT) with anthracyclines, whether cardiac protection with enalapril was started at study entry in all (prevention arm) or only upon first occurrence on supra-normal cTn (troponin-triggered arm). The aims of the present post hoc analysis were (i) to assess whether anthracycline-based treatment could induce cardiotoxicity over 36 month follow-up and (ii) to describe the time course of three cardiovascular biomarkers (i.e. troponin I cTnI-Ultra, B-type natriuretic peptide BNP, and pentraxin 3 PTX3) and of left ventricular (LV) function up to 36 months. METHODS AND RESULTS: Eligible patients were those prescribed first-in-life CT, without evidence of cardiovascular disease, normal cTn, LV ejection fraction (EF) >50%, not on renin-angiotensin aldosterone system antagonists. Patients underwent echocardiography and blood sampling at 24 and 36 months. No differences were observed in biomarker concentration between the two study arms, 'prevention' vs. 'troponin-triggered'. During additional follow-up 13 more deaths occurred, leading to a total of 23 (9.5%), all due to a non-cardiovascular cause. No new occurrences of LV-dysfunction were reported. Two additional patients were admitted to the hospital for cardiovascular causes, both for acute pulmonary embolism. No first onset of raised cTnI-Ultra was reported in the extended follow-up. BNP remained within normal range: at 36 months was 23.4 ng/L, higher (N.S.) than at baseline, 17.6 ng/L. PTX3 peaked at 5.2 ng/mL 1 month after CT and returned to baseline values thereafter. cTnI-Ultra peaked at 26 ng/L 1 month after CT and returned to 3 ng/L until the last measurement at 36 months. All echocardiographic variables remained stable during follow-up with a median LVEF of 63% and left atrial volume index about 24 mL/m2 . CONCLUSIONS: First-in-life CT with median cumulative dose of anthracyclines of 180 mg/m2 does not seem to cause clinically significant cardiac injury, as assessed by circulating biomarkers and echocardiography, in patients aged 51 years (median), without pre-existing cardiac disease. This may suggest either a 100% efficacy of enalapril (given as preventive or troponin-triggered) or a reassuringly low absolute cardiovascular risk in this cohort of patients, which may not require intensive cardiologic follow-up.

Androgen Receptor Expression and Association With Distant Disease-Free Survival in Triple Negative Breast Cancer: Analysis of 263 Patients Treated With Standard Therapy for Stage I-III Disease.

Background: We evaluated immunohistochemical AR expression and correlation with prognosis in a large series of homogeneously treated patients with primary TNBC. Material and Methods: Patients diagnosed with stage I-III TNBC between 2000 and 2015 at Istituto Oncologico Veneto who received treatment with surgery and neoadjuvant and/or adjuvant chemotherapy were included. Whole tissue slides were stained for AR. AR-positive expression was defined as >1% of positively stained tumor cells. Distant-disease-free survival (DDFS) was calculated from diagnosis to distant relapse or death. Late-DDFS was calculated from the landmark of 3 years after diagnosis until distant relapse or death. Results: We included 263 primary TNBC patients. Mean AR expression was 14% (range 0-100%), and 29.7% (n = 78) of patients were AR+. AR+ vs. AR- cases presented more frequently older age (p < 0.001), non-ductal histology (p < 0.001), G1-G2 (p = 0.003), lower Ki67 (p < 0.001) and lower TILs (p = 0.008). At a median follow up of 81 months, 23.6% of patients experienced a DDFS event: 33.3% of AR+ and 19.5% of AR- patients (p = 0.015). 5 years DDFS rates were 67.2% and 80.6% for AR+ and AR- patients (HR = 1.82 95%CI 1.10-3.02, p = 0.020). AR maintained an independent prognostic role beyond stage, but when TILs were added to the model only stage and TILs were independent prognostic factors. AR was the only factor significantly associated with late-DDFS: 16.4% of AR+ and 3.4% of AR- patients experienced a DDFS after the landmark of 3 years after diagnosis (p = 0.001). Late-DDFS rates at 5 years from the 3-year landmark were 75.8% for AR+ and 95.2% for AR- patients (log-rank p < 0.001; HR = 5.67, 95%CI 1.90-16.94, p = 0.002). Conclusions: AR expression is associated with worse outcome for patients with TNBC. In particular, AR+ TNBC patients are at increased risk of late DDFS events. These results reinforce the rationale of AR targeting in AR+ TNBC.

Management of Frail and Not-Frail elderly cancer patients in a hospital-based geriatric oncology program.

PURPOSE: To evaluate management and outcome of patients >or=70 years admitted to our Medical Oncology ward and evaluated by Multidimensional Geriatric Assessment before treatment with standard or "elderly-friendly" chemotherapy regimens, a list of which was developed within our Geriatric Oncology Program based on published clinical trials and personal experience. PATIENTS AND METHODS: Charts of patients treated from January 2004 to January 2006 were reviewed for choice of treatment, tumor response, toxicities and survival. RESULTS: 117 patients (median age 75 years) were divided into Frail (F) (34.2%) and Not-Frail patients (NF: 33.3% Fit plus 32.5% Vulnerable). The two groups did not differ according to the use of "elderly-friendly"chemotherapy regimens (40% of F pts and 39% of NF pts), dose reductions >or=25% (37.5% vs. 31.2%) and grade 3-4 toxicities (52.5% vs. 58.4%). Early interruption of treatment due to toxicity or patient's refusal (42.5 vs. 15.6, p=0.001) and deaths within 30 days from last chemotherapy administration (22.5% vs. 3.9%, p=0.003) were significantly different. F patients showed clinical or radiological response in 21.2% of cases, and subjective improvement in 22.6%. After a median follow-up of 19 months, median survival of F patients (6.4 months) is shorter compared to NF group (16.9 months, p=0.012). CONCLUSIONS: The use of "elderly-friendly"chemotherapy regimens was limited to less than a half of cases. F patients may respond to chemotherapy but display higher rates of premature withdrawal and early deaths compared to NF patients, with a shorter survival. Clinical trials particularly aimed at frail patients are urgently needed.

Adjuvant treatment for elderly patients with colon cancer. An observational study.

BACKGROUND: Adjuvant 5-fluoruracil-based chemotherapy significantly reduces mortality in patients with stage II-III colon cancer, but is less prescribed with rising age. In this study we were interested in the pattern of adjuvant treatment and possible effects on survival among elderly patients. PATIENTS AND METHODS: From January to December 2004, 63 questionnaires on the management of stage II-III resected colon cancer patients aged over 70 years, collected from 10 Italian Centres, were retrospectively examined. Determinants of receipt of adjuvant chemotherapy and their relation to survival were considered. RESULTS: The proportion of elderly patients receiving adjuvant chemotherapy was 79.4%, distinct of age, gender, educational level and comorbidities. Grade 3-4 toxicities were the following: haematological in 4 (8.5.%) patients, mucositis in 4 (8.5%), diarrhoea in 2 (4.2%) and nausea in 1 (2.1%). The disease-free survival (DFS) and overall survival (OS) at two years were 79.9% and 95.6%, respectively. Due to the paucity of events, the impact of prognostic factors (patient's age and comorbidity, tumour stage and grade) on DFS and OS could not be assessed. CONCLUSION: An increasing proportion of elderly patients with colon cancer may be treated with a tolerability and OS similar to those observed in the younger population. Development of age-based guidelines and increased awareness of both physicians and patients through education is important to prevent undertreatment of those elderly patients who are eligible for chemotherapy.

Palliative treatment for elderly patients with colon cancer in ten Italian medical oncology units.

BACKGROUND: Palliative chemotherapy significantly reduces mortality in patients with stage IV colon cancer, but is less prescribed with rising age. In this paper, we highlight the pattern of palliative treatment and possible effects on survival among elderly patients. PATIENTS AND METHODS: From January to December 2004, 78 files on the management of stage IV colorectal cancer (CRC) patients over 70 years, collected from 10 Italian Centres, were retrospectively examined. Determinants of receipt of palliative chemotherapy and their relation to toxicity and survival were considered. RESULTS: The proportion of elderly patients receiving first-line palliative chemotherapy was 98.7% and it was evaluated according to age, gender, educational level and comorbidities; patients receiving second-line therapy comprised 47.4%, those receiving third-line therapy 14.1% and those treated with a fourth-line therapy totalled 2.6%. Forty-one percent of patients received best supportive care (BSC) alone. CONCLUSION: In Italy, a proportion of elderly patients with metastatic chemonaive CRC are usually treated with a tolerability and overall survival similar to those for the younger population. Among progressive patients after second-line therapy, 45.8% usually undergo third line therapy; the remaining 54.2% undergo BSC.

Anthracycline-induced cardiotoxicity: A multicenter randomised trial comparing two strategies for guiding prevention with enalapril: The International CardioOncology Society-one trial.

BACKGROUND: Troponin changes over time have been suggested to allow for an early diagnosis of cardiac injury ensuing cancer chemotherapy; cancer patients with troponin elevation may benefit of therapy with enalapril. It is unknown whether a preventive treatment with enalapril may further increase the benefit. METHODS: The International CardioOncology Society-one trial (ICOS-ONE) was a controlled, open-label trial conducted in 21 Italian hospitals. Patients were randomly assigned to two strategies: enalapril in all patients started before chemotherapy (CT; 'prevention' arm), and enalapril started only in patients with an increase in troponin during or after CT ('troponin-triggered' arm). Troponin was assayed locally in 2596 blood samples, before and after each anthracycline-containing CT cycle and at each study visit; electrocardiogram and echocardiogram were done at baseline, and at 1, 3, 6 and 12-month follow-up. Primary outcome was the incidence of troponin elevation above the threshold. FINDINGS: Of the 273 patients, 88% were women, mean age 51 ± 12 years. The majority (76%) had breast cancer, 3% had a history of hypertension and 4% were diabetic. Epirubicin and doxorubicin were most commonly prescribed, with median cumulative doses of 360 [270-360] and 240 [240-240] mg/m2, respectively. The incidence of troponin elevation was 23% in the prevention and 26% in the troponin-triggered group (p = 0.50). Three patients (1.1%) -two in the prevention, one in the troponin-triggered group-developed cardiotoxicity, defined as 10% point reduction of LV ejection fraction, with values lower than 50%. INTERPRETATION: Low cumulative doses of anthracyclines in adult patients with low cardiovascular risk can raise troponins, without differences between the two strategies of giving enalapril. Considering a benefit of enalapril in the prevention of LV dysfunction, a troponin-triggered strategy may be more convenient.

Gemcitabine in advanced biliary tract cancers.

The annual incidence of hepatobiliary cancer has been steadily increasing in the USA from 15,000 in 1993 to 22,200 in 2000. Despite this increase, it still continues to be a rare neoplasm. Surgical resection is the treatment of choice, but a high percentage of patients are unsuitable for resection. These patients have a very poor prognosis because of the lack of efficacious therapy options. Thus, overall survival in these patients ranges from 3 to 12 months, depending on the extent of disease and its site of origin. For some time, mitomycin C, doxorubicin and 5-fluorouracil have been considered among the most active chemotherapeutic agents, with a response rate ranging from 10 to 20%. More recently, gemcitabine has become the reference agent for these neoplasias because of the histologically common origin of biliary cancer and exocrine pancreatic cancer. However, its role has yet to be well-defined. Here we examine clinical trials designed for locally advanced and metastatic biliary tract cancer and review the existing data supporting palliative therapy with gemcitabine alone or in association with other drugs.

Quality of life in elderly cancer patients.

The incidence of most types of cancer is age-dependent and progressive ageing is rapidly increasing the number of elderly people who need treatment for cancer. Elderly patients (older than 70 years) present particular characteristics that make the choice of the correct treatment more difficult; for this reason, these patients are often undertreated and largely underrepresented in cancer trials making the experimental evidence on this topic even weaker. Only relatively recently has Health-Related Quality of Life (HRQoL) begun to be considered as one of the hard end-points for clinical cancer research in the elderly. Treatment of elderly cancer patients represents a typical situation where its assessment is particularly useful because of the expected toxicity of treatment and several unresolved methodological problems (higher frequency of illiteracy, worse compliance with the questionnaires, concomitant diseases, use of instruments not validated in the aged population). The aim of this review is to underline the importance detected by the too small number of studies on elderly QoL evaluation and the need in future trials either to improve QoL assessment in this subcategory of patients undergoing treatment for cancer or not, or find specific assessment tools to do it.