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Introduction Obesity is a known independent risk factor for endometrial cancer (EC), and obese patients have a 4.7-fold increased risk compared to the general population to develop the neoplasm. To date, a general pre and postoperative tumor grading agreement from 53 % to 82 % is reported for endometrial analysis, and a consensus on which factors might influence the tumor grading discordance is still absent. Furthermore, although obesity alters the endometrial microenvironment, no studies investigated the role of obesity in the grading agreement of EC patients. This study aims to analyze the role of obesity in the pre and postoperative tumor grading agreement. Materials and methods A retrospective analysis was conducted on EC cancer women subjected to surgical treatment. Upgrading discordance was defined as higher tumor grading on final pathological analysis compared to tumor grading on the preoperative examination. Downgrading discordance was defined as a lower tumor grading at the postoperative surgical specimen analysis compared to the preoperative biopsy. Results Of the 293 selected patients, 245 were included in the analysis. One hundred and forty nine (60.8 %) patients were tumor grade G1, 52 (21.2 %) G2, and 44 (18.0 %) G3. Grading agreement was 83.9 % for G1 patients, 51.9 % for G2 patients, and 83.3 % for G3 patients. The multivariate analysis showed obesity (BMI > 30 kg/m2) as significant factor influencing pre and postoperative grading agreement (p = 0.014, Odds Ratio 2.036, 95 % Confidence Interval 1.141–3.635). Conclusions Our study for the first time showed obesity as the only factor in the multivariate analysis lowering the pre and postoperative tumor grading concordance. Grade 2 tumor was the factor that most frequently disagreed with the final surgical specimen analysis both in the general and in obese patients.

Interventional oncology plays a major role within modern oncological patient management. Image-guided thermal ablation has been recognized as a successful local therapeutic option in patients with primary and secondary malignant liver diseases, as also recalled by the recent European Society of Medical Oncology (ESMO) guidelines on colorectal metastases. As image-guided treatments may be as effective as surgery in selected patients with liver lesions, the clinical oncologist should be familiar with the indications, risks, and technical aspects of liver ablation in order to provide their patients with the best outcomes. This article provides a broad overview of the most commonly used ablation techniques and highlights the most relevant technical aspects such as the ideal setting in the operating theatre; which image-guided methods are available, including the growing application of fusion imaging; or contrast-enhanced ultrasound for guiding/monitoring the procedure. A further aim is to expand the knowledge among medical oncologists about liver ablation procedures and to provide insights into the future perspectives of percutaneous minimally invasive procedures in the liver.

Objective This review aims to analyze the pathological aspects, diagnosis and treatment of rare mesenchymal uterine tumors. Methods On August 2019, a systematic review of the literature was done on Pubmed, MEDLINE, Scopus, and Google Scholar search engines. The systematic review was carried out in agreement with the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes statement (PRISMA). The following words and key phrases have been searched: "endometrial stromal sarcoma", "low-grade endometrial stromal sarcoma", "high-grade endometrial stromal sarcoma", "uterine sarcoma", "mesenchymal uterine tumors" and "uterine stromal sarcoma". Across these platforms and research studies, five main aspects were analyzed: the biological characteristics of the neoplasms, the number of cases, the different therapeutic approaches used, the follow-up and the oncological outcomes. Results Of the 94 studies initially identified, 55 were chosen selecting articles focusing on endometrial stromal sarcoma. Of these fifty-five studies, 46 were retrospective in design, 7 were reviews and 2 randomized phases III trials. Conclusion Endometrial stromal sarcomas are rare mesenchymal uterine neoplasms and surgery represents the standard treatment. For uterus-limited disease, the remove en bloc with an intact resection of the tumor (without the use of morcellation) is strongly recommended. For advanced-stage disease, the standard surgical treatment is adequate cytoreduction with metastatectomy. Pelvic and para-aortic lymphadenectomy is not recommended in patients with Low-grade Endometrial Stromal Sarcoma (ESS), while is not clear whether cytoreduction of advanced tumors improves patient survival in High-grade ESS. Administration of adjuvant radiotherapy or chemotherapy is not routinely used and its role is still debated.

Simple Summary The treatments for patients with oligometastatic colorectal carcinoma are rapidly evolving. The present review focuses on the role of minimally invasive techniques since they can now be used as an alternative to surgical management in selected cases in association with systemic therapies according to ESMO and NCCN guidelines. In recent years, biomarkers (both at molecular and imaging level) have emerged as a relevant and potential criteria for treatment strategy decision and will be crucial in the future for patients selection. Tumor molecular profile impacts on local outcome of image guide ablation as well as metabolic imaging which predicts the outcome of both percutaneous and trans-arterial treatments. Oncologists should be aware of advantages and disadvantages of those treatments options as well as the potential role of molecular profile for a better patient selection. Abstract Colorectal cancer (CRC) is the third most common cancer worldwide and has a high rate of metastatic disease which is the main cause of CRC-related death. Oligometastatic disease is a clinical condition recently included in ESMO guidelines that can benefit from a more aggressive locoregional approach. This review focuses the attention on colorectal liver metastases (CRLM) and highlights recommendations and therapeutic locoregional strategies drawn from the current literature and consensus conferences. The different percutaneous therapies (radiofrequency ablation, microwave ablation, irreversible electroporation) as well as trans-arterial approaches (chemoembolization and radioembolization) are discussed. Ablation margins, the choice of the imaging guidance as well as characteristics of the different ablation techniques and other technical aspects are analyzed. A specific attention is then paid to the increasing role of biomarkers (in particular molecular profiling) and their role in the selection of the proper treatment for the right patient. In conclusion, in this review an up-to-date state of the art of the application of locoregional treatments on CRLM is provided, highlighting both technical aspects and the role of biomarkers, two sides of the same coin.

Background Lower muscle mass is a known predictor of unfavorable outcome, but its prognostic impact on COVID-19 patients is unknown. Purpose To investigate the contribution of CT-derived muscle status in predicting clinical outcomes in COVID-19 patients. Materials and Methods Clinical/laboratory data and outcomes (intensive care unit [ICU] admission and death) were retrospectively retrieved for patients with reverse transcriptase polymerase chain reaction-confirmed COVID-19, who underwent chest CT on admission in four hospitals in Northern Italy from February 21 to April 30, 2020. Extent and type of pulmonary involvement, mediastinal lymphadenopathy, and pleural effusion were assessed. Cross-sectional areas and attenuation of paravertebral muscles were measured on axial CT images at T5 and T12 vertebral level. Multivariable linear and binary logistic regression, including calculation odds ratios (OR) with 95% confidence intervals (CIs), were used to build four models to predict ICU admission and death, tested and compared using receiver operating characteristic curve (ROC) analysis. Results A total 552 patients (364 men; median age 65 years, interquartile range 54-75) were included. In a CT-based model, lower-than-median T5 paravertebral muscle area showed the highest ORs for ICU admission (OR 4.8, 95% CI 2.7-8.5; P

Purpose A multidimensional prognostic index (MPI) based on a comprehensive geriatric assessment (CGA) has been developed and validated in independent cohorts of older patients demonstrating good accuracy in predicting one-year mortality. The aim of this study was to develop a cancer-specific modified MPI (Onco-MPI) for mortality prediction in older cancer patients. Methods We enrolled 658 new cancer subjects ≥70 years (mean age 77.1 years, 433 females, 65.8 %) attending oncological outpatient services from September 2004 to June 2011. The Onco-MPI was calculated according to a validated algorithm as a weighted linear combination of the following CGA domains: age, sex, basal and instrumental activities of daily living, Eastern Cooperative Oncology Group performance status, mini-mental state examination, body mass index, Cumulative Illness Rating Scale, number of drugs and the presence of caregiver. Cancer sites (breast 46.5 %, colorectal 21.3 %, lung 6.4 %, prostate 5.5 %, urinary tract 5.0 %, other 15.3 %) and cancer stages (I 37 %, II 22 %, III 19 %, IV 22 %) were also included in the model. All-cause mortality was recorded. Three grades of severity of the Onco-MPI score (low risk: 0.0–0.46, medium risk: 0.47–0.63, high risk: 0.64–1.0) were calculated using RECPAM method. Discriminatory power and calibration were assessed by estimating survival C-indices, along with 95 % confidence interval (CI) and the survival-based Hosmer–Lemeshow (HL) measures. Results One-year mortality incidence rate was 17.4 %. A significant difference in mortality rates was observed in Onco-MPI low risk compared to medium- and high-risk patients (2.1 vs. 17.7 vs. 80.8 %, p

Some parameters of the Comprehensive Geriatric Assessment (CGA) are predictive of chemotherapy toxicity. The Vulnerable Elders Survey-13 (VES-13) is a short instrument that has been tested as a means of identifying patients who need a full CGA, but its ability to predict chemotherapy toxicity is still unclear. We performed a pooled analysis of four published clinical trials studying VES-13 as a means of diagnosing vulnerability, in order to evaluate its accuracy in predicting the risk of grade 3/4 toxicity in older patients undergoing chemotherapy.The study involved patients aged ≥ 66 years with a diagnosis of solid or hematological cancer, all of whom were administered VES-13. The number of medications taken by each patient, their comorbidities, their Cumulative Illness Rating Scale for Geriatrics (CIRS-G) score and index, the type of chemotherapy and treatment line, and their Mini Mental State Evaluation (MMSE), and Mini Nutritional Assessment (MNA) scores were recorded. Information was available concerning the grades 3-4 hematological and non-hematological toxicities experienced by each patient.The study involved 648 patients aged ≥ 66 years (mean age 76.2±4.5, range 66-90) of whom 336 (51.9%) were female. VES-13 identified 287 patients (44.3%) as vulnerable. Grades 3-4 hematological and non-hematological toxicities were more prevalent in the vulnerable subjects (35.2% vs 20.8%, p0.0001, and 18.5% vs 10.8%, p=0.0055), who were also at higher risk of both (adjusted ORs 2.15, 95% CI 1.46-3.17, p0.001); and 1.66 (95% CI 1.02-2.72, p=0.043).VES-13 could be considered to be a good candidate for future prospective studies to assess older patients with cancer at risk of toxicity.

Background: Currently, the acquisition of tissue from metastatic deposits is not recommended as a routine practice. Our aim was to evaluate the discordance rate of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) receptor status between primary tumor and liver metastases and its potential impact on treatment choice. Patients and methods: Weretrospectively analyzeda database including1250ultrasound-guided liverbiopsies carried out at the European Institute of Oncology from August 1999 to March 2009. ER, PgR, and HER2 status were determined by immunohistochemistry and/or FISH. Differences between proportions were evaluated using Fisher's exact test. Results: We identified 255 consecutive patients with matched primary and liver tissue samples. Changes in ER status were observed in 37 of 255 patients (14.5%). Changes in PgR status were observed in 124 of 255 patients (48.6%). Changes in HER2 status were observed in 24 of 172 assessable patients (13.9%). We observed a discordance in receptor status (ER, PgR, and HER2) between primary tumor and liver metastases, which led to change in therapy for 31 of 255 of patients (12.1%). Conclusions: Biopsy of metastases for reassessment of biological features should be considered in all patients, when safe and easy to carry out, since it is likely to impact treatment choice. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Purpose Cisplatin and temozolomide (TMZ) are active in glioblastoma multiforme (GBM), with different profiles of toxicity. A bid regimen of TMZ achieves a strong inhibition of O6-alkylguanine DNA-alkyl transferase (AGAT), and cisplatin reduces AGAT activity in vitro, suggesting a possible synergic interaction. The primary end point of the present multicenter phase II study was progression-free survival (PFS) at 6 months (PFS-6); secondary end points included response, toxicity, and overall survival. Patients and Methods Chemotherapy-naive patients with GBM who experienced disease recurrence or progression after surgery and standard radiotherapy were eligible. Chemotherapy cycles consisted of cisplatin 75 mg/m2 on day 1, TMZ 130 mg/m2 bolus followed by nine doses of 70 mg/m2 every 12 hours (total of 5 days) from day 2 every 4 weeks. In the absence of hematologic toxicity, TMZ was escalated to 1,000 mg/m2 in 5 days. Results A total of 50 patients (median age, 53.4 years; range, 27 to 70 years; median Karnofsky performance status, 80; range, 60 to 100) were accrued in the study. PFS-6 was 34% (95% CI, 23% to 50%), and PFS-12 was 4% (95% CI, 0.3% to 16%). Median PFS was 18.4 weeks (95% CI, 13 to 25.9 weeks). Among 49 assessable patients, one complete response and nine partial responses were obtained, with an overall response rate of 20.4% (95% CI, 7.7% to 33%). Among 203 treatment cycles delivered, the most common grade 3 or grade 4 events included granulocytopenia in 7.9% of cycles, thrombocytopenia in 4%, and neurologic toxicity in three patients (6%). Conclusion The new cisplatin plus bid TMZ regimen appears active in chemotherapy-naive patients with recurrent GBM and incurs an acceptable toxicity.

Objectives To investigate a comprehensive geriatric assessment (CGA) with subsequent investigation of healthcare patterns in older patients with urological cancers undergoing initial surgery or radiotherapy, to verify the usefulness of the incorporation of geriatric principles in future care plans. Material and Methods This is a prospective cohort study. From November 2011 to March 2015, CGA was offered to all patients aged 70+ years treated with radiotherapy or surgery at seven tertiary centers. Patients were classified as fit, vulnerable, or frail according to Balducci's definition. CGA and follow-up data were collected by two trained evaluators at 6 and 12months. The information collected was not available to the caring physicians during follow-up. Results CGA was performed in 453 patients with prostate cancer (295), bladder cancer (126), or kidney cancer (32). 40% of patients with prostate cancer were fit, 47% vulnerable, and 13% frail. The corresponding values for renal cancer were 25%, 40%, and 34%, and for bladder cancer, 21%, 42%, and 37%. During follow-up, 60% of patients with cardiac diseases, 42% of those with diabetes/other metabolic disorders, 35% of those with hypertension, and 35% of those with respiratory diseases were followed by a specialist (for these severe/extremely severe comorbidities). Of 16 patients with ADL impairment and 63 with IADL impairment, only 4 (25%) and 6 (10%), respectively, were referred to a rehabilitation service. Only one case was referred to a geriatrician. Conclusions Appropriate clinical care patterns are advisable to improve quality of survivorship in older patients with urological cancers.

The Multidimensional Geriatric Assessment (MGA) is currently used for assessing geriatric oncological patients, but a new prognostic index - the Multidimensional Prognostic Index (MPI) - has a demonstrated prognostic value in cancer patients too. The present work was designed to compare the MPI and MGA as predictors of 12-month mortality. 160 patients ≥70 years old with locally-advanced or metastatic solid cancers consecutively joining our Geriatric Oncology Program were administered a Comprehensive Geriatric Assessment to calculate their MGA and MPI scores. Settings: Geriatric Clinic, Geriatric Surgery Clinic, Medical Oncology Unit, Padova Hospital, Italy. Using Cohen's Kappa coefficient, there was a poor concordance between the MPI and MGA. Severe MPI being associated with a higher mortality risk than Frail in the MGA. The ROC curves indicated that the MPI had a greater discriminatory power for 12-month mortality than the MGA. In our population of elderly cancer patients, the MPI performed better than the MGA in predicting mortality. Further evidence from larger prospective trials is needed to establish whether other geriatric scales, such as the GDS and CIRS-SI, could enhance the value of prognostic indexes applied to elderly cancer patients.

A considerable knowledge has been collected in the last 20 years through retrospective and prospective trials on the medical management of cancer in older patients. Today a better approach to prevention and treatment of chemotherapy-related complications in older patients is provided by specific guide-lines.In this review, a synthetic information on the medical treatment specifically required by patients with age associated conditions for the most common tumor types (breast, non-small-cell lung prostate, colrectal cancer, and aggressive non-Hodgkin's lymphoma) is presented.

Prostate cancer is the most prevalent cancer in men and predominantly affects older men (aged ≥70 years). The median age at diagnosis is 68 years; overall, two-thirds of prostate cancer-related deaths occur in men aged ≥75 years. With the exponential ageing of the population and the increasing life-expectancy in developed countries, the burden of prostate cancer is expected to increase dramatically in the future. To date, no specific guidelines on the management of prostate cancer in older men have been published. The International Society of Geriatric Oncology (SIOG) conducted a systematic bibliographic search based on screening, diagnostic procedures and treatment options for localized and advanced prostate cancer, to develop a proposal for recommendations that should provide the highest standard of care for older men with prostate cancer. The consensus of the SIOG Prostate Cancer Task Force is that older men with prostate cancer should be managed according to their individual health status, which is mainly driven by the severity of associated comorbid conditions, and not according to chronological age. Existing international recommendations (European Association of Urology, National Comprehensive Cancer Network, and American Urological Association) are the backbone for localized and advanced prostate cancer treatment, but need to be adapted to patient health status. Based on a rapid and simple evaluation, patients can be classified into four different groups: 1, ‘Healthy’ patients (controlled comorbidity, fully independent in daily living activities, no malnutrition) should receive the same treatment as younger patients; 2, ‘Vulnerable’ patients (reversible impairment) should receive standard treatment after medical intervention; 3, ‘Frail’ patients (irreversible impairment) should receive adapted treatment; 4, Patients who are ‘too sick’ with ‘terminal illness’ should receive only symptomatic palliative treatment.

Elderly women constitute a large group of breast cancer patients, and after multidimensional geriatric assessment (MGA) only a minor part of them are found in perfect health (=fit), while the remaining display one or more physical or functional limitations or familial/social problems and are therefore categorized as vulnerable or frail (=unfit). Although randomized trials have not produced modest evidence that surgery impacts on ultimate survival of elderly women with hormone-responsive tumors, there is a general consensus that age alone should not prevent surgical local treatment even in unfit women due to the limited morbidity of breast surgery and to the risk of local progression. Activity and safety of AIs appear comparable in elderly women compared to younger counterparts, although concomitant cardiovascular comorbidity and osteoporosis should be closely monitored. Of note, compliance to oral therapy in unfit women and possible interferences with concomitant medications are still poorly documented issues. With the exception of high-risk node positive and estrogen-receptor negative patients, administration of adjuvant chemotherapy for estrogen-receptor positive unfit patients is rarely recommended since the uncertain gain in relapse-free survival is exceeded by the increased risk of toxicity and competitive causes of death. Endocrine-responsive metastatic disease is managed with one or more lines of endocrine treatment as in younger patients. Single agent sequential chemotherapy regimens are to be preferred to combination regimens, which are usually more toxic with a limited survival gain even in younger patients. When and how dose reductions should be applied to unfit patients is highly controversial. Trastuzumab in association with chemotherapy can be administered to elderly patients presenting HER2 overexpressing tumors, although the risk of cardiac adverse events in unfit patients is largely unknown. Bevacizumab-based combinations increase the activity and also toxicity of taxane chemotherapy, and are not a preferred option.

Prostate cancer is largely a disease of older men, with more than 90% of mortality observed in patients over 65 years. In the metastatic setting, a number of treatment options are available, with androgen-deprivation therapy being the first-choice, but few studies have examined the feasibility and efficacy of endocrine therapy and chemotherapy in men aged 70 years or older. Since the preservation of quality of life is the main objective of treatment in metastatic prostate cancer, every therapeutic decision should be conditioned by results of a geriatric comprehensive assessment.

The surgical treatment of colon cancer in elderly patients (aged 70 years or older) has improved, but data on adjuvant and palliative chemotherapy tolerability and benefits in this growing population remain scarce. Elderly patients are under-represented in clinical trials and results for older patients are seldom reported separately. However, elderly patients with good performance status tolerate adjuvant and palliative chemotherapy for colon cancer as well as their younger patients, and have similar benefits from palliative chemotherapy. This article examines the factors pertinent to the small number of trials designed for colon cancer in this group of persons.

Breast cancer is the most common malignancy in women worldwide, and represents the leading cause of death in the female population. Incidence of breast cancer increases with age, and older patients are more likely to have disseminated disease at diagnosis. The majority of breast cancer in older women is hormone-receptor positive, therefore, endocrine treatment with tamoxifen or aromatase inhibitors must be considered as first choice. For those patients who relapse after endocrine treatment or in whom the tumor does not express hormone receptors, chemotherapy should be considered. Single-agent sequential regimens should be preferred to combination regimens, which are usually more toxic and provide a limited survival gain. Trastuzumab in association with chemotherapy can be administered to elderly patients who present with HER2-overexpressing tumors, although cardiac monitoring is necessary owing to cardiac adverse events. Some geriatric assessment tools could help in qualifying those patients who can be treated with conventional therapy from those who should receive adjusted regimens, and from those who are frail and should be managed with the best supportive care.

Purpose To evaluate management and outcome of patients ≥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 ≥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.

Epidermal growth factor receptor-overexpression reported in colorectal cancer, justifies therapeutic use of EGFR-inhibitors. We have recently conducted a phase II study in 57 patients with EGFR-positive advanced colorectal cancer (ACC) who received gefitinib-FOLFOX6 followed by gefitinib-single agent as maintenance. Main biological objective was to assess sEGFR as surrogate marker of tyrosine kinase inhibition and as predictor of response.sEGFR, evaluated by quantitative ELISA, was investigated as predictive factor both taking into account the basal value only, and its whole pattern over time. sEGFR was collected at baseline and at every 2-months assessment in 42 cases. Thirty-three patients reported CR/PR as best objective response (BOR), while nine showed SD/PD.Retrospectively, on average, the sEGFR values reported by both responders (CR/PR) and not responders (SD/PD) were already different at baseline (49.4 +/- 6.2 and 42.4 +/- 8.4 ng/ml respectively). This difference was statistically significant (p = 0.042). Although sEGFR trend over time confirmed the basal difference (p = 0.032), this result should be taken with caution, due to the small number of patients reporting EGFR values besides the basal one.Higher sEGFR at baseline was associated to BOR and may be considered a significant predictor of outcome in patients with ACC.

More than 30% of lung cancers arise in patients aged 70 years or more; however, because elderly patients are not considered to tolerate chemotherapy, they are generally excluded from clinical trials and are not considered eligible for aggressive cisplatin-based chemotherapy in clinical practice. The aims of the present study were to test tolerability and activity of weekly vinorelbine in advanced non-small cell lung cancer (NSCLC) patients aged 70 years or more, and to define whether minimum conditions existed for a randomised comparison with best supportive care. The study was designed as a multicentre two-stage phase II trial according to Simon's optimal design: 8 or more responses out of 43 treated patients were expected at the end of the trial. Patients aged 70 years or more were eligible if they had a cytological or histological diagnosis of NSCLC at stage IIIb–IV and a performance status less than or equal to two according to the ECOG scale. Vinorelbine was given intravenously (i.v.) at a dose of 30 mg/m 2 every week for 12 doses. As planned, 43 patients entered the study; median age was 73 years (range 70–80); 11 patients were older than 75 years. Median dose-intensity (mg/m 2 /week) of vinorelbine was 21.2 (range 7.5–30) and was not affected by age of patients. Toxicity was generally mild, mainly haematological and never life-threatening. ECOG performance status improved in 26% of patients; cough and pain improved in more than 40% of patients symptomatic at entry, while dyspnoea improved in 28%; approximately half the patients had a stabilisation of their symptoms. 10 patients (23–95% exact confidence interval (CI): 12–39%) obtained a partial response. Median time to progression was 11 weeks (95% CI 8–30) and median survival 36 weeks (95% CI 28–53). One-year estimated progression-free and overall survival rates are 16% and 36%, respectively. In conclusion, vinorelbine was well tolerated and active in the treatment of elderly NSCLC patients. A phase III trial (ELVIS—Elderly Lung Cancer Vinorelbine Italian Study) comparing best supportive care versus best supportive care plus vinorelbine is now ongoing.

To evaluate the toxicity and feasibility of pelvic radiotherapy (RT) and/or surgery in elderly patients with locally advanced low-lying rectal cancer.From November 1999 to November 2005, 51 patients agedor=70 years who underwent RT for locally advanced low-lying rectal cancer were retrospectively examined. Variables considered were age, co-morbidities (evaluated according to the Charlson score and the Cumulative Illness Rating Scale-Geriatric [CIRS-G] score) and surgery versus no surgery.The median age was 80 years (range 70-94 years) and the male : female ratio was 33 : 18. A total of 5.9% of patients were considered 'fit', 72.5% had one or more CIRS-G grade 1 or 2 co-morbidities and 21.6% had one or more CIRS-G grade 3 co-morbidities. 54.9% of patients underwent surgery and 45.1% underwent RT. Only 9 of 21 (42.8%) patients who underwent radical resection received the full course of adjuvant RT and only seven (50%) of all patients treated with RT alone received the full dose of therapy. Patients with one or more CIRS-G grade 3 co-morbidities reported similar numbers of grade 1-2 toxicities as patients with one or more CIRS-G grade 2 co-morbidities.Notwithstanding the small number of patients analysed, the findings of this study indicate that elderly patients with rectal cancer and mild co-morbidities could probably receive the same treatment as fit elderly patients, given that tolerability appeared to be similar in both categories of patients. Neither age nor co-morbidities should be considered reasons to deny the patient the possible benefits of receiving complete treatment. Moreover, Multidimensional Geriatric Assessment should always be undertaken to help clinicians make better decisions about treatment. Further prospective trials are needed to confirm these results.

The hypothesis that increasing cytotoxic dose intensity will improve cancer cure rates is compelling. Although supporting evidence for this hypothesis has accrued for several tumor types, including lymphomas, breast cancer, and testicular cancers, it remains unproven. Small-cell lung cancer is extremely chemo- and radiosensitive, with a response rate of 80% achieved routinely, but few patients are cured by chemoradiotherapy. In this setting, increased cytotoxic dose intensity might improve cure rates. The finding that response rates in small-cell lung cancer correlate with received cytotoxic dose intensity merely confirms that “less is worse” and “more is better.” Within conventional ranges, dose intensity can be increased with the support of hematopoietic growth factors and/or by shortening treatments intervals; however, dose intensity could be increased by only 20%–30%, and a survival advantage has not been clearly demonstrated. Given its high chemosensitivity, small-cell lung cancer was one of the first malignancies deemed suitable for increasing dose intensity and even for the use of a megadose with the support of autologous bone marrow transplantation. Some interest is emerging again due to improvements in supportive care, such as the availability of hematopoietic growth factors and peripheral blood progenitor cells.

Background. In patients with metastatic breast cancer, the evaluation of the biological characteristics of metastatic bone deposits may be a valuable adjunct in clinical practice. We assessed the discordance in expression levels for estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER2) between primary tumor and bone metastases and its clinical impact on patient management. Material and methods. We retrospectively reviewed 363 CT-guided bone biopsies performed from January 1997 to December 2009. The proportions of ER, PgR and HER2 positive tumors at primary diagnosis and bone metastases, determined by IHC and/or FISH, were compared using McNemar's test. The impact of the biopsy reassessment on treatment choice was evaluated with Fisher's exact test. Results. We selected 109 metastatic breast cancer patients with histologically confirmed bone metastases. Among 107 assessable patients the overall discordance rate was detected in 22 (20.5%) and in 47 (43.9%) patients for ER and PgR, respectively, and in six of 86 assessable patients (6.9%) for HER2 status. The indication to change endocrine therapy occurred in 62% and 30% of patients with ER discordance and ER concordance, respectively (p = 0.01). The indication to change targeted therapy occurred in 67% and 8% of patients with HER2 discordance and HER2 concordance, respectively (p = 0.002). Conclusions. We confirm that biopsy of metastases, including bone metastases, for reassessment of biology should be considered, since it is likely to impact on treatment choice.

The Italian Cooperative Group on AIDS & Tumors (GICAT) is collecting data on the epidemiological and clinical features of Kaposi's sarcoma (KS) in Italy, a country where intravenous drug users (IVDUs) comprise the largest group affected by AIDS. As of December 31st 1989, among 5317 cases of CDC-defined AIDS reported to the National Registry of AIDS, there were 419 (8%) cases of KS. Twenty-five percent of all of the homosexual men with CDC-defined AIDS had KS, while only 3% of the IVDU patients with CDC-defined AIDS had KS. The first case of KS was observed in 1982, 2 cases in 1983, 7 cases in 1984, 17 cases in 1985, 55 cases in 1986, 89 cases in 1987, 120 cases in 1988 and 128 cases in 1989. Of the 226 cases of KS reported to GICAT, 60% were in homosexual men, 21% in IVDUs, and 9% in heterosexuals. An increased number of KS has been observed since 1982, although the number of new cases in the past year seems to have been stable, possibly due to the usual delay in notification. There is, however, an actual decrease of the percentage of KS among AIDS patients, from 18% in 1984 to 6% in 1989. Almost half of the patients had had a diagnosis of AIDS prior to the appearance of KS, but in 25% of the patients KS was the first AIDS manifestation. Almost all patients had skin involvement either alone or in association with other sites, whereas very few patients had only lymph node involvement. Only treatment with alpha-2 interferon was able to obtain complete remission in 9% of evaluable patients.(ABSTRACT TRUNCATED AT 250 WORDS)

An open questionnaire on the management of older cancer patients in the Italian Divisions of Medical Oncology was sent to the Chiefs of the units in the last 4 months of the year 2004. One hundred and ninety-nine of 330 (60%) responded. The majority of the Medical Oncologists interviewed agreed that special therapeutic protocols were necessary for elderly cancer patients. Also specific guidelines were believed to be useful. In only a minority of units there were some members specifically dedicated to older patients and the Multidimensional Geriatric (MGE) was used routinely only in 12% of cases. The majority of the physicians interviewed believed that older patients accepted chemotherapy as the younger ones did, or even more (79%). Written informed consent was obtained in the majority of units (70%). Over 63% believed that oral antitumor drugs had a very important role in older patients, while 36% were sceptical or negative. More time and attention should be paid to older patients (87.4%) and more economic resources devoted to them (93.3%). In conclusion, Italian Medical Oncologists are well aware of the increasing number of old cancer patients, of the particular problems concerning drug administration and the need of specific trials and guidelines. The need of close contact with Geriatricians and the adoption of Geriatric tools (MGE) are only perceived by a minority. The majority, however, believes that more time and resources should be available in order to take care of elderly cancer patients.

Colorectal adenocarcinoma ranks second as a cause of death due to cancer in the Western world. In Europe, 40% of patients with this disease is over 70 years old and only 52% of them with positive nodes usually receive an adjuvant chemotherapy. Despite early reports to the contrary, these patients tolerate cancer treatment and surgical resections as well as their younger counterparts but as a result of exclusion criteria, those receiving an adjuvant therapy are very few. This paper examines the factors pertinent to the small number of clinical trials designed for adjuvant colorectal cancer in the elderly.

Although Kaposi's sarcoma (KS) has decreased in countries where the highly active antiretroviral therapy (HAART) regimen is available, however it remains, after non-Hodgkin's lymphomas, the most common malignancy in HIV+ patients. Advances in the treatment of AIDS-KS have been achieved, even though a gold standard therapy has not been yet defined. With the availability of HAART, a dramatic KS clinical response has been documented, making HAART essential in all patients. In case of aggressive and/or life threatening KS, more complex therapeutic schedules have to be taken into account, including chemotherapy and/or immunotherapy. Liposomal anthracyclines and paclitaxel have been approved by FDA as first line and second line mono-therapy, respectively. Interferon-alpha (INF-α) is the only immunomodulant agent to have shown a therapeutic effect. Among the new drugs, many antiangiogenetic agents have produced encouraging responses. Finally, the identification of the HHV-8 as a causative agent and new metalloproteinase inhibitors may offer promising targets for the KS treatment.

Bladder cancer is rare in patients below the age of 50 years, and most patients are in their 60s and 70s. Radical cystectomy is the preferred approach for patients with localized disease in most European countries and the USA, and evidence is growing in favor of neoadjuvant, platinum-based chemotherapy for patients at high risk of local and systemic relapse. Transurethral resection (TUR) followed by radiotherapy with or without concomitant chemotherapy appears to be a reasonable alternative, particularly in the UK and Canada. However, the elderly pose several treatment dilemmas, including the increased risk of perioperative complications, the management of orthotopic neobladder or different types of urinary diversion, as well as the higher risk of adverse events caused by pelvic radiotherapy and systemic chemotherapy. Multidimensional parameters such as biologic prognostic factors, performance status, functional independence, comorbidities and cognitive function of the patient should be collected in order to tailor treatment to the patient's life expectancy and preferences. Optimized integration of TUR followed by bladder removal (or radiotherapy), with or without adjunctive chemotherapy, can be recommended for otherwise healthy patients. Palliative measures, such as TUR followed by external radiotherapy alone or monochemotherapy, should be reserved for partially impaired patients with moderate comorbidities, in order to maximize the balance of benefits and toxicities. This review summarizes recent data concerning surgery, radiotherapy and systemic chemotherapy for bladder cancer in the elderly, and discusses pros and cons of the currently available therapeutic options.

Background This study was a phase II study of third-line chemotherapy with carboplatin plus teniposide in patients with recurrent oligodendroglioma. Patients and methods Patients with oligodendroglioma progressive or recurrent after surgery, radiotherapy and chemotherapy with PCV (lomustine/procarbazine/vincristine) and temozolomide were treated with 350 mg/m2 carboplatin on day 1, and 50 mg/m2 teniposide on days 1–3, every 4 weeks. Results Response and toxicity were evaluated in all 23 patients enrolled in the study. Two had partial response [8.6%; 95% confidence interval (CI) 1.8% to 28.6%] and 12 stable disease (52.17%; 95% CI 30% to 73%). Median time to progression was 19 weeks (95% CI 11.4–35.0), and 34.8% of the patients (95% CI 20.0% to 61.0%) had progression-free survival at 6 months. Median survival time was 60.7 weeks (95% CI 39.8 to not achieved) and 51% of the patients (95% CI 33.5% to 79.7%) were alive at 12 months. A total of 103 cycles were administered (on average 4.4 per patient; range 1–9). Toxicity was mild and mainly hematological, with grade 4 neutropenia and grade 4 thrombocytopenia in two (8.6%) and three patients (13%), respectively. Conclusions Although the response rate of combined carboplatin and teniposide chemotherapy in heavily pretreated oligodendroglial tumors is moderate, the toxicity is manageable, and delay of progression in responders or stable patients may still confer a relevant clinical benefit.

Purpose: Lonidamine (LND) can enhance the activity of anthracyclines in patients with metastatic breast cancer. A multicenter, prospective, randomized trial was designed to determine whether the association of LND with high-dose epirubicin plus cyclophosphamide (EC) could improve disease-free survival (DFS) in patients with early breast cancer (BC) compared with EC alone. Granulocyte colony-stimulating factor (G-CSF) was added to maintain the EC dose-intensity. Patients and Methods: From October 1991 to April 1994, 506 patients with stage I/II BC were randomly assigned to four groups: (A) epirubicin 120 mg/m2 and cyclophosphamide 600 mg/m2 administered intravenously on day 1 every 21 days for four cycles (124 patients); (B) EC plus LND 450 mg/d administered orally (125 patients); (C) EC plus G-CSF administered subcutaneously (129 patients); (D) EC plus LND plus G-CSF (128 patients). Results: Median follow-up was 55 months. Five-year DFS rate was similar for LND (B+D groups; 69.6%) versus non-LND arms (A+C groups; 70.3%) and G-CSF (C+D groups; 67.2%) versus non–G-CSF arms (A+B groups; 72.9%). Five-year overall survival (OS) was comparable in LND (79.1%) versus non-LND arms (81.3%) and in G-CSF (80.6%) versus non–G-CSF arms (79.6%). DFS and OS distributions in LND and G-CSF arms did not change according to tumor size, node, receptor, and menopausal status. G-CSF dramatically reduced hematologic toxicity without having a significant impact on dose-intensity (98.1% v 95.5% for C+D and A+B groups, respectively). Conclusion: EC is active and well tolerated in patients with early breast cancer. The addition of LND or G-CSF does not improve DFS or OS.

BACKGROUND Malignant pleural mesothelioma (MPM) is increasing rapidly worldwide. Currently, pemetrexed plus cisplatin chemotherapy showed a survival advantage versus cisplatin alone. No impact on patient survival of surgery, radiotherapy, or their combination has been demonstrated. METHODS Eight centers in northeastern Italy participated in a Phase II multicenter study. Chemotherapy was comprised of carboplatin area under the concentration-time curve 5 on Day 1 and gemcitabine 1000 mg/m2 on Days 1, 8, and 15. This cycle was repeated every 4 weeks. RESULTS Between July 1996 and September 2000, 50 patients were treated. Of the sample, 68% were males, 88% had a Eastern Cooperative Oncology Group performance status score of 0–1, 56% had Stage I–II disease, 68% had epithelioid histology, and 62% had no previous treatments. The delivered dose intensity of gemcitabine was 617 mg/m2 per week, which was 82% of the planned dose (750 mg/m2 per week). For carboplatin, the delivered dose intensity was 80 mg/m2 per week. Overall, 44% of 15th day doses were omitted or reduced. Twenty-six percent of the patients had partial responses (95% confidence interval: 15–40%) and 24% had disease progression. None of the patients had complete responses. The median response duration was 55 weeks (range, 13–113 weeks). Patients had good clinical benefit. For example, 46% had improved dyspnea, 40% improved in weight, and 26% experienced pain reduction. Patients developed Grade 3–4 leukopenia during 18 cycles (11%) of chemotherapy. Grade 3–4 thrombocytopenia occurred more frequently, i.e., there were 24 episodes (15%) among 17 patients. Grade 3 anemia developed among patients during eight cycles (5%). None of the patients developed Grade 3–4 nonhematologic toxicity. The median survival of this sample of patients was 66 weeks with 53%, 30%, and 20% of patients alive at 1, 2, and 3 years, respectively. The median progression-free survival period was 40 weeks. CONCLUSIONS The gemcitabine/carboplatin combination is a valid option in the treatment of MPM due to its acceptable toxicity profile, the good response rate, and the clinical benefit to patients. Minor adjustments in schedule (3-week cycles instead of 4-week cycles) would permit a more optimal treatment administration. Cancer 2003;97:2791–7. © 2003 American Cancer Society. DOI 10.1002/cncr.11405

BACKGROUND Elderly patients (age > 65 years) with glioblastoma multiforme frequently are excluded from clinical studies, and prospective trials for patients with this age group do not exist to date. METHODS The authors conducted a prospective trial in 79 consecutive elderly patients with glioblastoma who underwent surgery and received radiotherapy (59.44 grays in 33 fractions; Group A; n = 24 patients) or received the same radiotherapy plus adjuvant chemotherapy with procarbizine, lomustine, and vincristine (PCV; lomustine 110 mg/m2 on Day 1, procarbazine 60 mg/m2 on Days 8–21, and vincristine 1.4 mg/m2 on Days 8 and 29 every 42 days; Group B; n = 32 patients), or received the same radiotherapy plus adjuvant temozolomide (150 mg/m2 for 5 days every 28 days; Group C; n = 22 patients). RESULTS The median time to disease progression (TTP) and median survival MST were 7.2 months (95% confidence interval [95%CI], 6.34–8.64) and 12.5 months (95%CI, 11.6–14.8), respectively. The TTP was significantly better for Group C compared with Groups A and B (10.7 months vs. 5.3 months and 6.9 months, respectively; P = 0.0002). Karnofsky performance status (KPS) (P < 0.001) and temozolomide (P < 0.001) were the only independent prognostic factors. Overall survival was better in Group C compared with Group A (14.9 months vs. 11.2 months; P = 0.002), but there were no statistical differences found between Groups A and B or between Groups B and C. Only KPS (P < 0.001) was predictive of overall survival, even if temozolomide chemotherapy was very close to the significance level (P = 0.058). Hematologic Grade 3–4 toxicity was higher with the PCV chemotherapy regimen compared with the temozolomide chemotherapy regimen. CONCLUSIONS Age alone should not preclude appropriate treatment in elderly patients with good performance status, for whom definitive radiation therapy and adjuvant chemotherapy with temozolomide is advised. Cancer 2003;97:657–62. © 2003 American Cancer Society. DOI 10.1002/cncr.11097

PURPOSE To evaluate the efficacy and side effects of psolaren with ultraviolet light A (PUVA) and interferon-alpha-2a (IFN-α-2a) in patients with mycosis fungoides (MF) and Sezary syndrome (SS). PATIENTS AND METHODS From May 1993 to January 1999, 63 symptomatic patients with all stages of MF and SS were treated in a prospective Phase II trial with systemic escalating doses of IFN-α-2a combined with PUVA for 1 year, followed by indefinite PUVA maintenance in complete responding patients. RESULTS Sixty-three patients were enrolled (Stage IA, n = 6; IB, n = 37; IIA, n = 3; IIB, n = 3; III, n = 12; IVA, n = 2). Ten patients had received previous therapy. The median follow-up duration for the entire cohort is 37 months. Of 63 patients, 51 achieved a complete response (CR; 74.6%) or partial response (PR; 6%) to therapy. The median response duration is 32 months. The 5-year overall survival rate is 91% and the 5-year disease-free survival rate is 75%. No life-threatening side effects were observed. Five patients stopped IFN-α-2a therapy due to toxicity. Eighty-four percent of the patients received more than 75% of the planned dose (12 million units three times a week). CONCLUSIONS This combination of IFN-α-2a and phototherapy is an effective and safe therapy for patients with symptomatic MF. Cancer 2002;95:569–75. © 2002 American Cancer Society. DOI 10.1002/cncr.10706

Nasal administration of synthetic CD4(+) epitopes of the acetylcholine receptor (AChR) prevents experimental myasthenia gravis (EMG) in C57Bl/6 mice, but not in IL4-deficient C57Bl/6 (IL4(-/-)) mice. Here we verify that nasal tolerance requires IL4, by showing that CD4(+) cells from C57Bl/6 mice treated nasally with a pool of AChR CD4(+) epitopes protected IL4(-/-) mice from EMG and caused a reduced production of anti-AChR antibody. CD4(+) cells from C57Bl/6 mice treated with unrelated peptides or sham-treated did not induce protection. CD4(+) cells from C57Bl/6 mice treated with just one AChR peptide protected IL4(-/-) mice from EMG without affecting antibody synthesis.

Women in general have a 10% risk of developing breast cancer and a 2-3% chance of ovarian cancer in their life-times. Mutations in BRCA-1 and BRCA-2 are present in only a small portion (5-10%) of all breast cancers. Carriers of mutations in these genes have a greater risk of cancer, especially before menopause in the case of BRCA-1 carriers. In addition, their risk of contralateral breast cancer is significantly higher than for the general population (4.2-53% vs. 2%). The grade of contralateral tumours in these patients is more aggressive. BRCA-2 hereditary breast cancer seems more heterogeneous than the BRCA-1 phenotype, and not clearly different from sporadic forms. However, since 20-30% of carriers of BRCA mutations never develop breast or ovarian cancer, there must be other 'risk modifiers'. Survival is better for carriers of hereditary ovarian cancer. Patients with these mutations are referred for genetic counselling, a complex process which includes: an informative dialogue between the proband and the geneticist, drawing up a family history, informed consent, evaluation of risk, genetic testing and possible involvement of healthy family members.

Ab to the acetylcholine receptor (AChR) cause experimental myasthenia gravis (EMG). Th1 cytokines facilitate EMG, whereas Th2 cytokines might be protective. IL-10 inhibits Th1 responses but facilitates B cell proliferation and Ig production. We examined the role of IL-10 in EMG by using wild-type (WT) C57BL/6 mice and transgenic (TG) C57BL/6 mice that express IL-10 under control of the IL-2 promoter. We immunized the mice with doses of AChR that cause EMG in WT mice or with low doses ineffective at causing EMG in WT mice. After low-dose AChR immunization, WT mice did not develop EMG and had very little anti-AChR serum Ab, which were mainly IgG1, whereas TG mice developed EMG and had higher levels of anti-AChR serum Ab, which were mainly IgG2, in addition to IgG1. At the higher doses, TG mice developed EMG earlier and more frequently than WT mice and had more serum anti-AChR Ab. Both strains had similar relative serum concentrations of anti-AChR IgG subclasses and IgG and complement at the muscle synapses. CD8+-depleted splenocytes from all AChR-immunized mice proliferated in the presence of AChR and recognized a similar epitope repertoire. CD8+-depleted splenocytes from AChR-immunized TG mice stimulated in vitro with AChR secreted significantly more IL-10, but less of the prototypic Th1 cytokine IFN-γ, than those from WT mice. They secreted comparable amounts of IL-4 and slightly but not significantly reduced amounts of IL-2. This suggests that TG mice had reduced activation of anti-Torpedo AChR Th1 cells, but increased anti-AChR Ab synthesis, that likely resulted from IL-10-mediated stimulation of anti-AChR B cells. Thus, EMG development is not strictly dependent on Th1 cell activity.

Objective. Data concerning optimal treatment of elderly patients with ovarian cancer are scanty. The management of ovarian cancer in the aged patient is many-sided: the diagnosis can be difficult and delayed, and aggressive surgery is often not attempted because of concomitant morbidity. We tested a combination of carboplatin and mitoxantrone potentially associated with low toxicity in elderly patients with ovarian cancer. Methods. Eighty-two patients older than 70 years (median age, 75; range, 70–88) with epithelial ovarian cancer were referred to our multicenter group and enrolled into this pilot study. Carboplatin (JM8) was given at the dose of 230 mg/m 2 and mitoxantrone at the dose of 9 mg/m 2 every 28 days. Results. Dose-limiting toxicity was represented by 4 cases of thrombocytopenia and 1 case of gastrointestinal toxicity. These 5 episodes occurred in 328 assessable cycles, representing a low toxicity profile (3%). Of the 68 assessable patients, 36 (53%) did not respond to chemotherapy (no change + progressive disease), complete response was observed in 15 (22%), and partial remission was observed in 16 (23.5%), accounting for an overall response rate of 45%. Conclusion. The carboplatin–mitoxantrone combination, at the dosage tested in this study, appears to be well tolerated by elderly patients with advanced ovarian cancer and is associated with an acceptable response rate. Optimally debulked patients also showed improved survival when compared with patients with more extensive tumor.

Summary Background To investigate the efficacy of temozolomide in relation to response rate, toxicity, time to progression, and median survival time, a phase II study was conducted in patients with recurrent high-grade glioma following surgery plus radiotherapy and first-line chemotherapy based on nitrosourea, procarbazine and vincristine. Patients and methods Forty-one patients with high-grade glioma, at second recurrence or progression, of which twenty-two (54%) had glioblastoma multiforme, ten (24%) anaplastic astrocytoma, and nine (22%) anaplastic oligodendroglioma were administered temozolomide, 150 mg/m2/daily for five days every four weeks. Results Response was assessed in 40 patients. The overall response rate (complete + partial response) was 22.5% (95% confidence interval (CI): 9.5%–35%). The median time to progression for all 41 patients was 22.3 weeks; progression-free survival at 6 and 12 months was 48.5% and 34.7%, respectively. Median survival time was 37.1 weeks with 80.2% at 6 and 34.9% survival at 12 months. Conclusions On multivariate analysis, response to previous treatment was significant (P = 0.03) for time to progression and Karnofsky performance score for overall survivall (P = 0.002). Temozolomide gave a moderate response rate with acceptable toxicity as second-line chemotherapy in patients with recurrent high-grade glioma.

Despite the growing number of elderly patients currently receiving radiotherapy little is known about the side-e€ects and outcome of radiation in this group of population. Several retrospective studies indicate that outcome of elderly patients with cancer regarding local control and survival is comparable to younger patients, with the exception of aged patients with rectal carcinoma and high grade glioma which is perhaps caused by the less aggressive combined modality treatment given to these patients. The incidence of primary malignant brain tumours and mortality amongst the elderly in developed countries have increased dramatically during the last 3 decades [1,2]. Some authors suggested that the gene pool of surviving 75 year old individuals in 1994 is di€erent from the gene pool of surviving 75 year old individuals in 1900 indicating genetic factors are involved in the pathogenesis of primary brain tumours, the aggregate surviving gene pool of an ageing population cohort is important [3]. The relationship between age and outcome may, in part, re ect the greater proliferative potential of malignant glioma in older patients [4]. The role of radiotherapy, for patients with malignant gliomas, after whatever the type and extent of surgery, radical resection, partial resection or biopsy, is a recognised and unquestioned treatment, well established in randomised trials during the late 1970s [5,6]. Age, as well as histology, performance status scored by the Karnofsky performance scale (KPS) and extent of surgery, is one of the established prognostic factors [7±9]. When we evaluate the outcome of aged patients in clinical trials, we ®nd a speci®c problem in relation to age; as age of 65 years often represents a cut-o€ point for clinical trials. Furthermore, the majority of studies regard age as a split prognostic factor for analysis at the age of 50 years. An analysis of 1578 patients accrued from three successive Radiotherapy Oncology Group (RTOG) trials, with a top age limit of eligibility of 70 years, concluded that age under or over 50 years was the most important factor that distinguished patients with malignant glioma [7]. So elderly patients are not speci®cally approached. Most reports available consider the value of surgery and radiotherapy to be of questionable bene®t, although resection plus radiation doubles the mean length of postoperative survival [10]. Some studies have analysed the outcome of elderly patients with conventional treatment [11], pointing out that elderly patients with good performance status when treated with maximal resection and radiation have longer survival than those treated with a palliative intent with radiation therapy and biopsy, suggesting that intensive or radical treatment in this subset of population should be considered. Others reported that increasing age and poor neurological condition predict poor survival [12]. High grade gliomas are amongst the most devastating malignancies with few useful treatment options. Radiotherapy remains the most e€ective treatment modality in high grade glioma. Modem radiotherapy techniques to spare normal brain tissue when treating a tumour with a margin according to magnetic resonance imaging (MRI) image or computer tomography (CT) scan o€ers a survival bene®t, and in patients without extreme functional impairment the quality of life is good. Future studies in the treatment of central nervous system (CNS) tumours should include full evaluation of the patient functional status [13]. Patients with brain tumours have multiple functional disorders a€ecting mobility, communication, cognitive function and per

The incidence of central nervous system neoplasias ranges from 3.8 to 5.1 cases per 100,000 inhabitants. First-line treatment of brain tumors consists of surgery associated with radiotherapy, and followed or not by chemotherapy. When used as an adjuvant therapy after surgery and radiotherapy, chemotherapy prolongs the time to progression and the median survival time. At relapse, chemotherapy is the common therapeutic approach. In recent years, new drugs for the treatment of brain tumors have been tested, and some of them, such as temozolomide, are very promising.

Endocrine alterations are frequently found in patients undergoing treatment for CNS tumors. Careful follow-up aimed at the early detection of recurrences, with life-long monitor of hypothalamus–pituitary (HP) function, will also reveal any endocrine dysfunctions; indeed, their appropriate diagnosis and treatment may determine a significant improvement in the quality of life of these patients.

Purpose Small-cell lung cancer (SCLC) is increasingly diagnosed in elderly patients, who are at higher risk of treatment-related morbidity and mortality. We conducted a randomized two-stage phase II study to assess the therapeutic index of two different platinum/etoposide regimens, attenuated-dose (AD) and full-dose (FD) plus prophylactic lenograstim. Patients and Methods SCLC patients older than 70 years were randomized to receive four courses of cisplatin 25 mg/m2 on days 1 and 2, and etoposide 60 mg/m2 on days 1, 2, and 3 every 3 weeks (AD); or cisplatin 40 mg/m2 on days 1 and 2, and etoposide 100 mg/m2 on days 1, 2, and 3 every 3 weeks, plus lenograstim 5 mg/kg days 5 through 12, every 3 weeks (FD). A combined primary end point named therapeutic success (TS), which took into account activity, toxicity, and compliance, was used. Results Ninety-five patients were enrolled. Seventy-five percent and 72% of the patients in the AD and FD arms, respectively, completed the treatment as per protocol. Response rate was 39% and 69% in the AD and FD arms, respectively, and 1-year survival probability was 18% and 39%, respectively. Treatment was well tolerated in both groups, with no grade 3 to 4 myelotoxicity in the AD arm, and 12% myelotoxicity in the FD arm. Overall, the observed TSs were 10 (36%) of 28 patients and 42 (63%) of 67 patients for AD and FD treatments, respectively. Conclusion In elderly patients with SCLC a full-dose cisplatin/etoposide regimen combined with prophylactic lenograstim is active and feasible, while attenuated doses of the same regimen are associated with a poor therapeutic outcome.

Purpose To study the prognostic value for overall survival of baseline assessment of functional status, comorbidity, and quality of life (QoL) in elderly patients with advanced non—small-cell lung cancer treated with chemotherapy. Patients and Methods Data from 566 patients enrolled onto the phase III randomized Multicenter Italian Lung Cancer in the Elderly Study (MILES) study were analyzed. Functional status was measured as activities of daily living (ADL) and instrumental ADL (IADL). The presence of comorbidity was assessed with a checklist of 33 items; items 29 and 30 of the European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire QLQ-C30 (EORTC QLQ-C30) were used to estimate QoL. ADL was dichotomized as none versus one or more dependency. For IADL and QoL, three categories were defined using first and third quartiles as cut points. Comorbidity was summarized using the Charlson scale. Analysis was performed by Cox model, and stratified by treatment arm. Results Better values of baseline QoL (P = .0003) and IADL (P = .04) were significantly associated with better prognosis, whereas ADL (P = .44) and Charlson score (P = .66) had no prognostic value. Performance status 2 (P = .006) and a higher number of metastatic sites (P = .02) also predicted shorter overall survival. Conclusions Pretreatment global QoL and IADL scores, but not ADL and comorbidity, have significant prognostic value for survival of elderly patients with advanced non—small-cell lung cancer who were treated with chemotherapy. Using these scores in clinical practice might improve prognostic prediction for treatment planning.

The toxicity and therapeutic activity, including the effect on quality of life, of the carboplatin-oral etoposide combination, given with an intrapatient dose escalation, was tested in 38 non-small cell lung cancer (NSCLC) patients aged over 70 years, and in 8 younger patients with a performance status of 2. In the absence of grade 3-4 toxicity, doses were escalated as follows: first course (carboplatin AUC 4; etoposide 50 mg twice daily orally days 1-14); second course (carboplatin AUC 5; etoposide 50 mg twice daily orally days 1-14); third course (carboplatin AUC 5; etoposide 50 mg twice daily orally days 1-21). A total of 141 chemotherapy cycles were delivered. The treatment was, in general, well tolerated and no toxic deaths occurred. More than 60% of patients received 100% of the planned dose intensity. Transient grade 4 neutropenia or thrombocytopenia occurred in 6 and 2 patients, respectively, but only 2 patients had to be hospitalised because of fever. All patients were evaluated for activity on an 'intention to treat basis'. Ten partial responses and 20 stable disease were recorded, for an overall response rate of 22% (95% confidence interval (CI) = 11-36). 9/38 (24%; 95% CI = 12-41) elderly patients obtained a partial response. The median response duration was 4 months. A quality of life improvement was observed in 19 of the 46 enrolled patients (41%; 95% CI = 27-57), and 15/46 (33%; 95% CI = 19-48) showed a performance status improvement. The quality of life score improved in 17/38 (45%) elderly patients. 8/10 responders and 11/20 patients with stable disease showed a concomitant improvement in quality of life. At a median potential follow-up of 16 months (range 2-21), 31 patients had had progression of disease and 23 had died, for a median time to progression (TTP) and overall survival (OS) of 5 and 10 months, respectively. The median survival time was 11 months in the elderly patients. The median time to subjective impairment (TSI) was 6 months (7 months in the elderly group). One-year estimated TTP, TSI and OS rates were 22, 29 and 41%, respectively. At multivariate Cox analysis, a > 25% improvement in the quality of life score was more predictive of a better survival outcome than the response achievement.