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.

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.

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.

Follow-up of elderly patients with urogenital cancers: Evaluation of geriatric care needs and related actions.

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.

Development of an oncological-multidimensional prognostic index (Onco-MPI) for mortality prediction in older cancer patients.

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 < 0.0001). The discriminatory power of one-year mortality prediction of the Onco-MPI was very good (survival C-index 0.87, 95 % CI 0.84-0.90) with an excellent calibration (HL p value 0.854). CONCLUSION: Onco-MPI appears to be a highly accurate and well-calibrated predictive tool for one-year mortality in older cancer patients that can be useful for clinical decision making in this age group.

Estimating the risk of chemotherapy toxicity in older patients with cancer: The role of the Vulnerable Elders Survey-13 (VES-13).

OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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%, p<0.0001, 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, p<0.001); and 1.66 (95% CI 1.02-2.72, p=0.043). CONCLUSIONS: VES-13 could be considered to be a good candidate for future prospective studies to assess older patients with cancer at risk of toxicity.

Does the Multidimensional Prognostic Index (MPI), based on a Comprehensive Geriatric Assessment (CGA), predict mortality in cancer patients? Results of a prospective observational trial.

OBJECTIVE: Despite the lack of definitive data on the impact of Comprehensive Geriatric Assessment (CGA) in the geriatric oncology setting, the broad use of any form of CGA is strongly recommended before any treatment decision in elderly cancer patients (ECP); currently there is no consensus about the best format for this geriatric assessment. The aim of this study was to firstly test the Multidimensional Prognostic Index (MPI) in ECP with locally advanced or metastatic disease. MATERIALS AND METHODS: Patients aged ≥70years with inoperable or metastatic solid cancer consecutively admitted to our Program of Geriatric Oncology were assessed by a multidisciplinary team and received a basal CGA to calculate the MPI score. RESULTS: A hundred and sixty patients entered the study. In the Cox's regression model, MPI, CIRS-SI, BSA, GDS, MMSE, chemotherapy and a diagnosis of primary lung cancer were associated with mortality at 6 and 12months. The ROC curves confirmed the prognostic value of MPI, with the best discriminatory power for mortality at both 6 and 12months. CONCLUSION: The present study is the first to indicate that the MPI retains its prognostic value even in elderly cancer patients with advanced stage of disease. The CIRS-SI and the GDS may potentiate the prognostic value of MPI.

Bi-weekly liposomal doxorubicin for advanced breast cancer in elderly women (≥ 70 years).

BACKGROUND: We conducted a multicenter prospective trial to assess tolerability and activity of pegylated liposomal doxorubicin (PLD) in women ≥ 70 years with locally-advanced or metastatic breast cancer. PATIENTS AND METHODS: All patients underwent Multidimensional Geriatric Assessment (MGA). Frail patients were excluded. Normal cardiac function was required for inclusion. A bi-weekly schedule of PLD at 20mg/mq was adopted. RESULTS: Thirty-two patients were enrolled with a median age of 78 years, 78.1% with visceral involvement, and 37.6% previously treated with chemotherapy for advanced disease. A mean of 7.8 cycles were delivered (range 1 to 20), with a median cumulative dose intensity of 8.9 mg/m(2)/week. Grade 3-4 toxicities were anemia (6.3%), palmar-plantar erythrodysesthesia (6.3%), mucositis (6.3%), infection (3.1%), and pulmonary embolism (3.1%). No cardiac events were registered. Causes of treatment interruption were maximal response (15.6%), progression (40.6%), refusal/loss to follow-up (28.1%), toxicities (9.4%), or other (6.3%). Response was obtained in 33.3% of 27 evaluable patients; median time to progression (TTP) was 10.3 months. MGA status (vulnerable vs. fit) did not have an impact on response, progression, and toxicity. CONCLUSIONS: Bi-weekly PLD is well tolerated in both fit and vulnerable patients, with an apparently fairly good response rate and TTP (possibly biased by subsequent endocrine therapy and loss to follow-up). Close observation of patients is recommended in order to avoid early refusal/loss to follow-up.

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.

Cancer in the elderly.

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.

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.

Background for the proposal of SIOG guidelines for the management of prostate cancer in senior adults.

BACKGROUND: The incidence of prostate cancer increases with age, with a median age at diagnosis of 68 years. Owing to increased life expectancy, the management of prostate cancer in senior adult men (i.e., aged 70 years or older) represents an important public health concern and a major challenge for the future. No specific guidelines have previously been published on the management of prostate cancer in older men. The SIOG has developed a proposal of recommendations in this setting. METHODS: A systematic bibliographical search focused on screening, diagnostic procedures, treatment options for localised, locally advanced and metastatic prostate cancer in senior adults was performed. Specific aspects of the geriatric approach were emphasised, including evaluation of health status (nutritional, cognitive, thymic, physical and psycho-social) and screening for vulnerability and frailty. Attention was drawn to the consequences of androgen deprivation and complications of local treatment, mainly incontinence. The collected material has been reviewed and discussed by a scientific panel including urologists, radiation oncologists, medical oncologists and geriatricians from both Europe and North America. RESULTS: The consensus is to use either European Association of Urology or National Comprehensive Cancer Network clinical recommendations for prostate cancer treatment and to adapt them to health status based on instrumental activities of daily living (IADL) and activities daily living (ADL), comorbidity evaluation by Cumulative Illness Scoring Rating-Geriatrics and screening for malnutrition. Patients in Group 1 (no abnormality) are 'fit' and should receive the same treatment as younger patients; patients in Group 2 (one impairment in IADL or one uncontrolled comorbidity or at risk of malnutrition) are 'vulnerable' and should receive standard treatment after medical intervention; patients in Group 3 (one impairment in ADL or more than one uncontrolled comorbidity or severe malnutrition) are 'frail' and should receive adapted treatment; patients in Group 4 (dependent) should receive only symptomatic palliative treatment. CONCLUSIONS: Treatment of prostate cancer in senior adults should be adapted to health status. Specific prospective studies in this setting are warranted.

Management of primary and advanced breast cancer in older unfit patients (medical 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.

Can we better manage Unfit older cancer patients?

The term Unfit refers to older cancer patients not amenable with standard treatment and needing therefore a modified or attenuated treatment or also not deserving an active therapeutic approach. To determine whether an old patient is Unfit a Multidimensional Geriatric Evaluation is needed, but to spare time, shortened tools of evaluation are now in a phase of development. Most of the available data on older cancer patients derive from clinical prospective studies carried out in a selected population, with the exclusion then of Unfit patients. The challenge of this special issue of CTR is that of providing a clinically useful information on the basis of the results of the available studies and expert opinion in the main tumor types.

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.