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The knowledge of Geriatric Oncology requires some information on her history.Thanks to the effort of investigators throughout the world, embattled but undeterred by the objection of a cautious establishment, geriatric oncology has provided a blueprint for the treatment of the most common form of cancer: cancer in the older person. The history of Geriatric Oncology may be divided in three periods: Prehistory,Past and Contemporay history.

An oncogeriatric interdisciplinary activity exists only in a minority of high-income countries, and it is almost absent in those with lower incomes. Considering topics, sessions, and tracks in the main meetings and conferences of the major Oncological Societies in Europe and worldwide, the USA excluded, little attention has thus far been paid to the problem of cancer in the elderly. Again, with the exception of the USA, the major cooperative groups, for example, the EORTC in Europe, have only dedicated marginal attention to the research of cancer in the elderly. Despite major shortcomings, professionals interested in geriatric oncology have taken a number of important initiatives to highlight the benefits of this particular activity, including the organization of an international society (Société Internationale de Oncogeriatrie, or SIOG). In spite of these efforts, the authors believe that the management of cancer in the older population is still encountering several important and generalized pitfalls. The main obstacle is the grossly inadequate number of geriatricians and clinical oncologists necessary to an integrated care of the ever-expanding aging population, but other hurdles have been reported. Additionally, the prejudice of ageism can lead to missing potential resources for the development of a generalized oncogeriatric approach.

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

Radiation oncology has the potential to be an excellent option for the frail elderly cancer patients because of its limited systemic toxicities. It can be effective for curative, prophylactic, disease control or palliative purposes. Currently about 60% of all cancer patients undergoing active treatment at some point receive radiation treatment. However, though widely used, there are limited clinical trials strictly designed for the elderly. This paper will review the key points in the assessment and treatment of elderly cancer patient including quality of life, active life expectancy, cognitive performance, frailty, sarcopenia and how the new technologies can help to reach the key goal of maintaining autonomy and independence for the elderly cancer patient.

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.

Objectives The complication rate, loco-regional responses and length of hospital stay were analyzed in patients with liver and kidney cancer older than 70 years treated with interventional oncology procedures. The findings from the older population were compared with the younger patients ( Materials and methods Prospectively collected data on patients who underwent hepatic artery embolization (with or without radiofrequency ablation) and kidney radiofrequency ablation were retrospectively analyzed. Complication rates, loco-regional responses and length of hospital stay for patients older and younger than 70 were compared. Results 163 patients were treated, 66 (40.5%) older and 97 (59.5%) younger than 70 years. The complication rate in patients older than 70 was 4.5% (3/66 pts) versus 3.1% (3/97 pts) (p = 0.69) in the younger age-group. The complication rates for the liver embolization group, liver embolization plus radiofrequency and kidney radiofrequency group were 2/90 pts (2.2%), 2/42 pts (4.8%) and 2/31 pts (6.5%), respectively (p = 0.46). Median hospital stay was three nights in both older and younger patients. Response rates were not significantly influenced by age. Conclusion Liver embolization with or without radiofrequency and renal radiofrequency are safe and effective in older patients. Age alone should not be considered a contraindication to treatment in carefully selected patients.

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.

The EORTC Cancer in the ElderlyTask Force (ETF) aims to develop, conduct, coordinate and stimulate research on elderly patients with cancer. Towards this goal, the ETF has established close interactions with disease-oriented EORTC groups by having representatives from most of these groups attend the ETF meetings. In addition, the ETF reviews every new protocol for elderly-specific questions within the protocol review process of the EORTC aiming to reduce ageism within study protocols. Since 2006, the ETF decided to focus on three aspects: open a discussion on specific methodology for clinical trials in the older population; create a common language for describing heterogeneity between older individuals, the EORTC minimal dataset for geriatric assessment in older cancer patients; and develop specific clinical trials in the older population. This article reports the achievements of the ETF in these three domains and discusses its future strategies.

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.

As a result of an increasing life expectancy, the incidence of cancer cases diagnosed in the older population is rising. Indeed, cancer incidence is 11-fold higher in persons over the age of 65 than in younger ones. Despite this high incidence of cancer in older patients, solid data regarding the most appropriate approach and best treatment for older cancer patients are still lacking, mostly due to under-representation of these patients in prospective clinical trials. The clinical behaviour of common malignant diseases, e.g. breast, ovarian and lung cancers, lymphomas and acute leukaemias, may be different in older patients because of intrinsic variation of the neoplastic cells and the ability of the tumour host to support neoplastic growth. The decision to treat or not these patients should be based on patients' functional age rather than the chronological age. Assessment of patients' functional age includes the evaluation of health, functional status, nutrition, cognition and the psychosocial and economic context. The purpose of this paper is to focus on the influence of age on cancer presentation and cancer management in older cancer patients and to provide suggestions on clinical trial development and methodology in this population. (C) 2010 Elsevier Ltd. All rights reserved.

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.

Cancer treatment has meant an increasingly prolonged survival of older cancer patients, often associated with a functional decline. Rehabilitation focuses on facilitating recovery of the ability to perform activities of daily living and on enhancing a patient’s quality of life. The rehabilitative program should be tailored to single-out elderly patients after an attentive evaluation of their needs and the assessment of clinical, psychological and social conditions through a comprehensive geriatric assessment. The evaluation of fatigue, pain, malnutrition, depression and cognitive impairment is essential in order to establish supportive therapies and improve compliance and outcomes. Rehabilitation care is performed with a multidisciplinary approach. Management consists of physical exercises and occupational therapy associated with specific organ rehabilitation, and is also related to the sequelae of treatments such as surgery, hormonotherapy and radiotherapy.

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.

The increasing number of elderly people in the world’s population has led to a parallel increase in the number of older cancer patients, with over 45% of all neoplasia in Europe occurring in patients older than 70 years. Rectal cancer is predominantly a disease of the elderly. Data emerging from cohort and retrospective studies show that elderly patients are less often treated with a multidisciplinary approach, including surgery, radiotherapy and chemotherapy, compared with their younger counterpart, probably based on the impression that older patients show poor tolerance and benefit less from the treatment. Any available analysis has confirmed this concern. Unfortunately, data from studies properly designed for the elderly are currently limited. This article focuses on the state-of-the-art approach in rectal cancer treatment and its role in older patients, focusing on how elderly differ from younger patients in terms of clinical presentation, access to multimodality programs, tolerance of the therapy and outcome.

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.

In dealing with older cancer patients undergoing chemotherapy, some form of geriatric evaluation is needed to distinguish those which can be treated as adults from those - the vulnerable ones - who need a modified approach and also from those who are frail or too sick to receive an active treatment. Only scarce data are available to guide treatment of vulnerable or frail patients, the neglected majority of older cancer patients. In most of these cases they receive an adapted approach which does not derive from the results of clinical trials, but from an enlightened empiricism. In this article we summarise and discuss available data for management of the main tumour types in frail and vulnerable patients, and call for further research in this field.

The incidence of most types of cancers is age-dependent and progressive ageing is rapidly increasing the number of elderly people who need treatment for cancer. It is an ethical dilemma how aggressive one should be when it comes to treating cancer in the older population. Presumed fear of increased postoperative morbidity and mortality often results in delivery of sub-optimal cancer surgery. A careful evaluation of the general and organ-related conditions of the patients is absolutely necessary for planning the right treatment. Nevertheless, preoperative removal of risk factors and postoperative rehabilitation are as important as the use of the best techniques of anaesthesia and surgery to achieve good postoperative outcomes in these patients. In this review article we take into consideration physiology of the aged and tools available to assess surgical risks in elderly patients, in the aim of increasing awareness on optimising surgical management of elderly patients with cancer. MEDLINE and EMBASE.com (search terms: "elderly", "preoperative", "surgery"), bibliographies of articles retrieved and the authors' reference files have been used as data sources. Independent extraction has been performed by the authors using predefined criteria, including study quality indicators.

The increasing number of elderly people in the world population has led to a parallel increase in the number of older cancer patients, with over 45% of all cancers in Europe occurring in patients >70 years of age. The increasing tendency to use oral chemotherapy is thus of interest in the elderly, given that both elderly patients and their physicians prefer to use less complex and toxic regimens when such treatments have equivalent efficacy to more complex regimens. However, data from studies designed to evaluate these therapies in the elderly are currently limited. Factors that must be considered before prescribing oral agents to this subset of patients include age-related physiological changes affecting clinical pharmacology, adherence, the patient's capability to self-administer medications, and safety issues concerning the older patient and his or her caregivers. The idea that elderly patients may benefit from the introduction of oral chemotherapy is very fashionable, but to date there is no proof that this approach is as effective as intravenous therapy in this age group, particularly since randomised trials are lacking. This review discusses these issues and reviews current information about the use of specific oral chemotherapeutic drugs for major neoplastic diseases in the elderly.

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.

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.

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.

Since September 1996, 48 untreated patients with bulky or advanced-stage Hodgkin’s disease received the 12-week Stanford V chemotherapy regimen followed by consolidation radiotherapy at a dose of 36 Gy to bulky mediastinal disease and 30.6 Gy to the initial sites of disease ≧3 cm in transverse diameter. After the combined therapy, 46 of 48 (96%) achieved complete remissions. With a median follow-up of 48 months, the 5-year overall survival was 95% and freedom from progression 86%.There were no treatment-related deaths. All but one premenopausal female patient (who received pelvic and inguinal irradiation) recovered normal menses. Until now no case of secondary leukemia or myelodysplasia was observed. Our results confirm that the Stanford V regimen with consolidation radiotherapy is safe and effective in patients with bulky or advanced-stage Hodgkin’s disease, achieving very high remission and overall 5-year survival rates. Longer follow-up is necessary to evaluate the extent of all complications.

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

Laura McGuinness, Commissioning Editor, speaks to Silvio Monfardini Professor Silvio Monfardini is currently the Chief of the Geriatric Oncology Program at the Istituto Palazzolo (Milan, Italy). Professor Silvio Monfardini is the author of over 500 publications, over 300 of which have been published in indexed journals. In the field of geriatric oncology he has produced 55 indexed publications. He is also the author of the ‘Manual of Medical Oncology (International Union Against Cancer)’ and has contributed to other oncology manuals and text books. Throughout his career Silvio Monfardini has worked in the fields of non-Hodgkin’s lymphomas, Hodgkin’s disease, chronic myeloid leukemia, solid tumors (in particular testicular carcinomas) Phase I–II studies and tumors in the elderly. In the year 2003–2004 he served as the President of the International Society of Geriatric Oncology (SIOG). In 2006, he received the Paul Calabresi award from the International Society of Geriatric Oncology. He is also a valuable member of the Aging Health editorial board.

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

From 1985 to 1998, at the Regional Cancer Center of Padua, patients with Hodgkin's disease (HD) routinely underwent a clinical staging procedure including lymphangiography and laparoscopy with multiple liver and spleen biopsies. Patients with IA and IIA nonbulky HD were treated with radiotherapy alone. The aim of this study is to analyze the efficacy of radiotherapy as radical treatment in this group of patients, and the role of lymphangiography and laparoscopy in the selection of patients with abdominal disease located to the spleen, liver, or the pelvic lymphatic chains. From January 1985 to January 1998, 94 previously untreated patients with biopsy-proven HD underwent clinical staging procedures consisting of history, physical examination, routine laboratory tests, chest radiography, total-body computed tomography scan, and bone marrow biopsy and were considered in stage I-IIA nonbulky. In addition, all patients underwent bipedal lymphangiography, which was positive in 12 (12.8%). Of the 82 patients with negative lymphangiography, 9 (11%) showed disease below the diaphragm at laparoscopy with multiple random spleen and liver biopsies. Of the remaining 73 patients, 32 were male and 41 were female with a median age of 29 years (range: 14-72 years). The stage at diagnosis was IA in 34 patients and IIA in 39. Histology was nodular sclerosis (NS) in 44 patients, lymphocyte predominance (LP) in 16, and mixed cellularity (MC) in 13. Of the 39 IIA stage patients, 27 showed an involvement of 2 lymph-nodal regions, 1 1 of 3 regions, and 1 of 4 regions. All patients were treated with radiotherapy alone for a total dose of 39.6 Gy in 22 fractions. Of the 39 IIA stage patients, 36 were treated with subtotal lymphoid irradiation (STLI), mantle plus paraaortic and spleen field, and 3 with mantle field alone, while of the 34 IA stage patients, 20 were treated with STLI, 13 with mantle field, and 1 with involved field. After a medium follow-up of 104 months (minimum 27, maximum 195, median 101), 71 patients (97%) are still alive without evidence of disease. Seven patients (10.4%) relapsed 3, 11, 12, 15, 28, 29, and 48 months after the diagnosis. Initially the stage of these patients was IA in 3 and IIA in 4, whereas the histology was NS in 5, LP in 1, and MC in 1. One patient alone had a pelvic failure, 48 months after the first diagnosis. The other sites of relapse were: bone marrow in 2 patients, bone marrow plus liver in 2, axillary nodes in 1, and internal mammary chain nodes in another. All relapsed patients had previously undergone subtotal lymphoid irradiation (STLI). At relapse, 5 patients received chemotherapy, 1 chemotherapy plus radiotherapy, and 1 radiotherapy alone. Five of 7 patients obtained a second complete remission still lasting after 27, 68, 70, 98, 103 months, respectively, whereas 2 patients (2.9%) died of progressive disease, respectively, 3 and 35 months after relapse. Our data suggest that a well-defined group of patients with early stage HD, who undergo an accurate clinical staging procedure, can be effectively treated with radiotherapy alone.

PURPOSE: To appraise the performance of Comprehensive Geriatric Assessment (CGA) in elderly cancer patients (≥ 65 years) and to evaluate whether it could add further information with respect to the Eastern Cooperative Oncology Group performance status (PS). PATIENTS AND METHODS: We studied 363 elderly cancer patients (195 males, 168 females; median age, 72 years) with solid (n = 271) or hematologic (n = 92) tumors. In addition to PS, their physical function was assessed by means of the activity of daily living (ADL) and instrumental activities of daily living (IADL) scales. Comorbidities were categorized according to Satariano’s index. The association between PS, comorbidity, and the items of the CGA was assessed by means of logistic regression analysis. RESULTS: These 363 elderly cancer patients had a good functional and mental status: 74% had a good PS (ie, lower than 2), 86% were ADL-independent, and 52% were IADL-independent. Forty-one percent of patients had one or more comorbid conditions. Of the patients with a good PS, 13.0% had two or more comorbidities; 9.3% and 37.7% had ADL or IADL limitations, respectively. By multivariate analysis, elderly cancer patients who were ADL-dependent or IADL-dependent had a nearly two-fold higher probability of having an elevated Satariano’s index than independent patients. A strong association emerged between PS and CGA, with a nearly five-fold increased probability of having a poor PS (ie, ≥ 2) recorded in patients dependent for ADL or IADL. CONCLUSION: The CGA adds substantial information on the functional assessment of elderly cancer patients, including patients with a good PS. The role of PS as unique marker of functional status needs to be reappraised among elderly cancer patients.

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.

BACKGROUND Recurrent central neurocytoma is very rare and to the authors' knowledge data regarding its response to chemotherapy currently are not available. METHODS Three patients with progressive neurocytoma received chemotherapy after their informed consent was obtained. Disease recurred in two patients after surgery and radiotherapy and in one patient after surgery. The treatment regimen was comprised of etoposide, 40 mg/m2/day, for 4 days; cisplatin, 25 mg/m2/day, for 4 days; and cyclophosphamide, 1000 mg/m2, on Day 4; this cycle was repeated every 4 weeks. RESULTS Stabilization of disease was observed in 2 patients and complete remission was observed in 1 patient; at last follow-up, these responses had been maintained for 15 months, 18 months, and 36 months, respectively. CONCLUSIONS In this small series, this therapeutic regimen led to long term disease reduction, and merits further study. Cancer 2000;88:169–74. © 2000 American Cancer Society.

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.