Pitfalls in Oncogeriatrics.

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.

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

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

Landmarks in geriatric oncology.

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.

Management of prostate cancer in older men: recommendations of a working group of the International Society of Geriatric Oncology.

Prostate cancer is the most prevalent cancer in men and predominantly affects older men (aged >or=70 years). The median age at diagnosis is 68 years; overall, two-thirds of prostate cancer-related deaths occur in men aged >or=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.

Older cancer patients and COVID-19 outbreak: Practical considerations and recommendations.

Since the COVID-19 outbreak started, it has been affecting mainly older individuals. Among the most vulnerable older individuals are those with cancer. Many published guidelines and consensus papers deal with prioritizing cancer care. Given the lack of high-quality evidence for management of cancer in older patients also in normal times, it is even more stringent to provide some resources on how to avoid both undertreatment and overtreatment in this population, who as of now is twice challenged to death, due to both a greater risk of getting infected with COVID-19 as well as from cancer not adequately addressed and treated. We hereby discuss some general recommendations (implement triage procedures; perform geriatric assessment; carefully assess comorbidity; promote early integration of palliative care in oncology; acknowledge the role of caregivers; maintain active take in charge to avoid feeling of abandonment; mandate seasonal flu vaccination) and discuss practical suggestions for specific disease settings (early-stage and advanced-stage disease for solid tumors, and hematological malignancies). The manuscript provides resources on how to avoid both undertreatment and overtreatment in older patients with cancer, who as of now is twice challenged to death, due to both a greater risk of getting infected with COVID-19 as well as from cancer not adequately addressed and treated.

Management of The Elderly Cancer Patients Complexity: The Radiation Oncology Potential.

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.

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

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

Vulnerable and frail elderly: an approach to the management of the main tumour types.

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.

Neoadjuvant chemoradiotherapy with 5-fluorouracil by bolus.

BACKGROUND: Neoadjuvant chemoradiotherapy (CT-RT) with continuous infusion (c.i.) 5-fluorouracil (5-FU) before resection of high-risk rectal cancer improves overall survival (OS) and pelvic control. Since the presence of cardiomiopathy may contraindicate c.i. of 5-FU, an alternative regimen of 5-FU CT-RT was prospectively studied in these patients. PATIENTS AND METHODS: From October 2000 to December 2006, patients with clinical stage T3 or T4, or node-positive disease were assigned according to their cardiological status to receive weekly 5-FU bolus administration during radiotherapy (RT). The preoperative treatment consisted of 5,040 cGy, delivered infractions of 180 cGy per day, five days per week, and 5-FU, given in 15 minutes at a dose of 450 mg/m2 of body surface area weekly during all radiotherapy. Surgery was performed six weeks after the completion of CT-RT. The primary endpoint was disease-free survival (DFS). RESULTS: Fifty-one patients received preoperative CH-RT. The 2-year OS rate was 92.3% and the 3-year DFS was 87.5%. The five-year cumulative incidence of local relapse was 3.9%. Grade 3 acute toxic effects occurred in 19.6% of the patients; worsening of patient's cardiopathy was never reported. CONCLUSION: Patients with cardiopathy developed similar local control and DFS, toxicity and OS with 5-FU administered weekly by bolus as those reported by literature data.

Role of neoadjuvant treatment in cT3N0M0 rectal cancer.

BACKGROUND: The aim of the study was to evaluate the pathological response (pTNM), local relapse and overall survival (OS) in clinical T3N0M0 (cT3N0M0) rectal cancer after a neoadjuvant chemoradiotherapy (CHT-RT) with 5-fluorouracil (5-FU) continuous infusion (c.i.) (+/- oxaliplatin) or bolus or capecitabine (an oral fluorpyrimidine). A secondary endpoint was to identify the local relapse rate and OS in those patients also receiving an adjuvant chemotherapy. PATIENTS AND METHODS: From January 2000 to January 2006, 48 consecutive cT3N0M0 rectal cancer cases neoadjuvantly treated were retrospectively examined. Variables considered were age, gender, modality of 5-FU administration and tumour site. RESULTS: Median age was 64 years (range, 22-84 years) and the male:female ratio was 28:20. All the patients received the full course of CHT-RT. Twenty-eight patients received c.i. 5-FU neoadjuvant chemotherapy, 17 received bolus 5-FU administration and 3 patients received capecitabine-based therapy. The mean number of chemotherapy weeks was 4.9 (range, 2-6). A total of 85.4% of patients were operated on without relevant postoperative complications but another 4 are awaiting surgery. Twenty-one patients had a lower (< or = 5 cm from the anal verge) and 27 had a middle rectal lesion (from 6 to 10 cm). In those patients with the lower site of lesion, a sphincter-saving (SS) procedure was achieved in 88.9%. Downstaging was reported in 66.7%. Ninety percent of cases are still free from progression after a median follow-up of 22.1 months; 7.5% are dead. CONCLUSION: The down-staging, the good level of SS and the disease-free survival (DFS) obtained here suggests that a neoadjuvant therapy may also be useful for stage II rectal cancer at diagnosis. The use of a postoperative chemotherapy should probably be outlined better.

Rectal cancer adjuvant chemotherapy: when is more useful?

UNLABELLED: THE AIM of the study was to evaluate time-to-progression (TTP) of rectal cancer in a group of patients receiving adjuvant chemotherapy (CHT) after combined neoadjuvant treatment. A secondary end-point was to identify the possible influence of clinical TNM (cTNM) or pathological TNM (pTNM) on TTP and overall survival (OS). PATIENTS AND METHODS: From January 2000 to December 2005, 101 consecutive rectal cancer patients who had been neoadjuvantly treated and had underne adjuvant CHT were retrospectively examined. The variables considered were age, gender and clinical and pathological effect of CHT administration. RESULTS: The mean age was 59 years (29-78 years) and the male:female ratio, 61:40. Forty-two patients had a lower (< or =5 cm from the anal verge), 54 a middle (from 6 to 10 cm) and 5 a higher (=10 cm) rectal lesion. All the patients had received the full course of neoadjuvant radiotherapy (RT) while 26.7% patients had received a reduced number of neoadjuvant CHT cycles. All the patients had undergone surgery and had received adjuvant chemotherapy which was completed in only 77.2% of the cases. Tumour down-staging and complete remissions were reported in 75.2% and 14.8% of cases, respectively. TTP and OS at 3 years were 81.2% and 91.1%, respectively. Out of locally recurrent patients, 77.8% were N+ (p=0.0026) at the pathological evaluation. CONCLUSION: In our series, neither administration of oxaliplatin-based adjuvant chemotherapy (p=0.44) nor age > or =70 years (p=0.51), clinical stage III (p=0.67), tumour down-staging (p=0.44) and achievement of pCR (p=0.66) appeared to have a significant impact on TTP; only pN+ (patients "not responders" to a neoadjuvant CHT-RT) influenced local relapse requiring more accurate postoperative treatment and confirming the literature data about the utility of adjuvant therapy in stage III disease.

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

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

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

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

Colorectal cancer screening in elderly patients: when should be more useful?

Current guidelines endorse colon cancer screening every 5-10 years in persons over 50 years of age. However, there is no consensus regarding what age is appropriate to stop screening. Prior history of neoplasia seems to be a strong risk factor for colorectal neoplasia development in elderly people and should be considered when deciding the need for continuing screening/surveillance, however, clinical judgment of comorbidities is still required to individualize screening practice. Screening colonoscopy in very elderly persons (aged 80 years), i.e. should be performed only after careful consideration of potential benefits, risks and patient preferences. The aims of this paper are to: (1) determine the best type of colorectal cancer screening (faecal occult blood testing, flexible sigmoidoscopy, double-contrast barium enema and colonoscopy) and its association with age and health status among elderly veterans and (2) describe the outcomes of colorectal cancer screening among older veterans who have widely differing life expectancies (based on age and health status).

Preoperative assessment of elderly cancer patients.

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.

Gemcitabine in advanced biliary tract cancers.

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

Organization of the clinical activity of geriatric oncology: report of a SIOG (International Society of Geriatric Oncology) task force.

Management for elderly cancer patients world wide is far from being optimal and few older patients are entering clinical trials. A SIOG Task Force was therefore activated to analyze how the clinical activity of Geriatric Oncology is organized. A structured questionnaire was circulated among the SIOG Members. Fifty eight answers were received. All respondents identified Geriatric Oncology, as an area of specialization, however the organization of the clinical activity was variable. Comprehensive Geriatric Assessment (CGA) was performed in 60% of cases. A Geriatric Oncology Program (GOP) was identified in 21 centers, 85% located in Oncology and 15% in Geriatric Departments. In the majority of GOP scheduled case discussion conferences dedicated to elderly cancer patients took regular place, the composition of the multidisciplinary team involved in the GOP activity included Medical Oncologists, Geriatricians, Nurses, Pharmacists, Social Workers. Fellowships in Geriatric Oncology were present in almost half of GOPs. Over 60% of respondents were willing to recruit patients over 70 years in clinical trials, while the proportion of cases included was only 20%. Enrolment in clinical trials was perceived as more difficult by 52% and much more difficult in 12% of the respondents. In conclusion, a better organization of the clinical activity in Geriatric Oncology allows a better clinical practice and an optimal clinical research. The GOP which can be set up in the oncological as well as in the geriatric environment thought a multidisciplinary coordinator effort. Future plans should also concentrate on divisions, units or departments of Geriatric Oncology.

Quality of life in elderly cancer patients.

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

Primary rectal carcinoma in patients with stage IV resectable disease at diagnosis.

BACKGROUND: Rectal cancer is commonly diagnosed at a precocious stage, but for patients presenting at diagnosis with stage IV disease the best treatment is still undefined. The purpose of this study was to review the feasibility and outcome of multimodality treatment of rectal cancer patients metastatic at diagnosis. PATIENTS AND METHODS: From January 2000 to December 2005, 40 patients with histologically proven stage IV rectal adenocarcinoma (< 12 cm from the anal verge) were examined. Variables considered were age (under or over 65 years), tumour grade, presence of peritoneal carcinomatosis, type of surgery (palliative versus resection). RESULTS: The median age was 61 years (range, 32-83) and 27 were male and 13 female. Seventeen patients with unresectable or potentially resectable metastatic disease received neoadjuvant chemoradiotherapy (CHT-RT) with 5-fluorouracil (5FU) (plus oxaliplatin in 11 cases), radical surgery was performed in almost half of the cases; only in two patients were metastases also resected. If the patient is a candidate for radical surgical resection, the primary tumour should initially be treated as in a patient without metastatic disease and subsequently the primary tumour and metastases should be treated surgically. If the metastases are unresectable, the treatment of the primary lesion, according to the patient's symptoms, should be by palliative CHT. It is still not determined whether RT should be reserved for the symptomatic cases as an alternative to local surgery. In five patients treated with neoadjuvant CHT alone, radical local surgery was performed in two cases. Eighteen symptomatic patients were resected primarily; all of them received a postoperative CHT but only five of them also received postoperative RT. Nevertheless, after a multimodality treatment (neoadjuvant CHT +/- RT) 22.5% achieved a response rate (RR) (one complete remission (CR) and eight partial remission (PR)). Considering that all except two of the patients were locally radically resected and two of them also underwent metastases surgery, the overall RR was 17.5% (four CR and three PR). All of the CR were disease-free and alive after a median follow-up of 19.3 months. Age > or = 65 years had no impact on overall survival (OS), but the presence of peritoneal carcinosis in five patients showed a trend towards diminished survival, although it was not statistically significant (p = 0.08). CONCLUSION: The best treatment on diagnosis of metastatic rectal cancer is a multimodality CHT-RT approach. New prospective studies should evaluate non cross-resistant regimens as additional therapy for those patients with a systemic residual disease after common CHT-RT.