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Cervical cancer is the fourth most common neoplasm in women. In locally advanced cervical cancers, the international guidelines recommend nodal aortic assessment. Two techniques have been described to perform laparoscopic aortic lymphadenectomy: transperitoneal laparoscopic lymphadenectomy (TLL) and extraperitoneal laparoscopic lymphadenectomy (ELL). This meta-analysis aims to compare the surgical outcomes of TLL and ELL for staging purposes. The systematic review was carried out in agreement with the preferred reporting items for systematic reviews and meta-analyses statement (PRISMA). Two hundred and twenty studies were analyzed, and 19 studies were included in the review (7 for TLL and 12 for ELL group). 1112 patients were included in the analysis: 390 patients were included in group 1 and 722 patients in group 2.38 patients (9.7%) in the TLL group and 69 (9.5%) patients in the ELL group developed major complications. The analysis of all complications (intraoperative and postoperative) rate through pooled analysis did not show a significant difference between the two groups (p = 0.979), although a significantly higher intraoperative complication rate (p = 0.018) occurred in the TLL group compared to ELL. No significant differences were found between groups for BMI (p = 0.659), estimated blood loss (p = 0.889), length of stay (p = 0.932), intraoperative time (p = 0.932), conversion to laparotomy rate (p = 0.404), number of lymph node excised (p = 0.461) and postoperative complication (p = 0.291). TLL approach shows a higher rate of intraoperative complications, while no significant difference was found between the two techniques when postoperative complications were analyzed.

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.

Background Based on patient and tumor characteristics, some authors favor laparoscopic microwave ablation (LMWA) over the percutaneous approach (PMWA) for treatment of hepatocellular carcinoma (HCC). We compared the two techniques in terms of technique efficacy, local tumor progression (LTP) and complication rates. Study design A retrospective comparative analysis was performed on 91 consecutive patients (102 HCC tumors) who underwent PMWA or LMWA between October 2014 and May 2019. Technique efficacy at one-month and LTP at follow-up were assessed by contrast-enhanced CT/MRI. Kaplan–Meier estimates and Cox regression were used to compare LTP-free survival (LTPFS). Results At baseline analysis, LMWA group showed higher frequency of multinodular disease (p

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.

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

The aim of the present study was to demonstrate the cost of obese patients affected by endometrial cancer undergoing open surgery compared with minimally invasive surgery. In the retrospective cohort study (Canadian Task Force classification II-2), the economic expenditure in pre-operative, intra-operative and post-operative phases of the selected patients was evaluated. Costs were analyzed for all blood tests, instrumental examinations, consultations, operating materials, drugs, gynecological examinations, hospital stay, intensive care hospitalization and management of operative complications. The average length of stay was longer for patients who underwent laparotomy, with an almost double median hospitalization cost in the open abdominal group compared with the laparoscopic group (€4,805.37 vs. €2,589.25; P

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.

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

Borderline ovarian tumors (BOT) represent 10-12% of ovarian cancer cases with a higher prevalence in young patients. Although reproductive outcomes are satisfactory after conservative treatment, several authors reported a higher relapse rate in patients undergoing fertility-sparing surgery compared with radical treatment. The aim of the present study was to identify predictive factors of BOT recurrence in patients with childbearing potential undergoing conservative treatment with unilateral salpingo-oophorectomy. From January 2010 to December 2020 all patients with childbearing potential undergoing conservative treatment for early-stage BOT were included in the analysis. Expert sonographers performed the ultrasounds and classified the ovarian lesion according to International Ovarian Tumor Analysis criteria. A total of 230 patients with BOT that underwent surgical treatment during the study period were analyzed. Of these, 82 patients met the inclusion criteria. Relapse was experienced in 11 cases (13.4%), one (1.2%) peritoneal surface and 10 (12.2%) recurrences on the contralateral ovary. Ovarian tumor size >50 mm (P=0.032; OR 7.317; 95% CI 0.89-60.29), multilocular cysts >10 loculi (P=0.016; OR 7.543; 95% CI 1.64-34.78), cysts with >4 papillae (P=0.025; OR 6.190; 95% CI 1.40-27.36) were statistically correlated with recurrent BOT. Overall, the present study showed that lesions with maximum diameter >50 mm (P=0.014), multilocular cysts >10 loculi (P=0.012) and cysts with >4 papillae (P=0.003) were independent predictive factors of BOT recurrence (P

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

Background Fluorouracil-based adjuvant chemotherapy in gastric cancer has been reported to be effective by several meta-analyses. Perioperative chemotherapy in locally advanced resectable gastric cancer (RGC) has been reported improving survival by two large randomized trials and recent meta-analyses but the role of neoadjuvant chemotherapy and optimal regimen remains to be determined. We compared a neoadjuvant with adjuvant docetaxel-based regimen in a prospective randomized phase III trial, of which we present the 10-year follow-up data. Patients and methods Patients with cT3–4 anyN M0 or anyT cN1–3 M0 gastric carcinoma, staged with endoscopic ultrasound, computed tomography, bone scan, and laparoscopy, were assigned to receive four 21-day/cycles of docetaxel 75 mg/m2 day 1, cisplatin 75 mg/m2 day 1, and fluorouracil 300 mg/m2/day over days 1–14, either before (arm A) or after (arm B) gastrectomy. Event-free survival was the primary end point, whereas secondary end points included overall survival, toxicity, down-staging, pathological response, quality of life, and feasibility of adjuvant chemotherapy. Results This trial was activated in November 1999 and closed in November 2005 due to insufficient accrual. Of the 70 enrolled patients, 69 were randomized, 34 to arm A and 35 to arm B. No difference in EFS (2.5 years in both arms) or OS (4.3 versus 3.7 years, in arms A and B, respectively) was found. A higher dose intensity of chemotherapy was observed in arm A and more frequent chemotherapy-related serious adverse events occurred in arm B. Surgery was safe after preoperative chemotherapy. A 12% pathological complete response was observed in arm A. Conclusion Docetaxel/cisplatin/fluorouracil chemotherapy is promising in preoperative setting of locally advanced RGC. The early stopping could mask the real effectiveness of neoadjuvant treatment. However, the complete pathological tumour responses, feasibility, and safe surgery warrant further investigation of a taxane-based regimen in the preoperative setting.

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

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

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.

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

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

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

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

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.

Background: Biopsies of metastatic sites are not recommended in clinical practice to evaluate changes in biological features in advanced breast cancer (ABC) women. We assessed discordance in expression levels for estrogen receptor (ER), progesterone receptor (PgR) and epidermal growth factor receptor 2 (HER2), between primary tumor and bone metastases and its clinical impact on patient management. Material and Methods: We retrospectively analyzed 109 ABC patients (pts) underwent computed tomography guided bone biopsy at the European Institute of Oncology in Milan, Italy, from 1997 to 2009. Data on ER and PgR status [positive if ≥1% by immunohistochemistry (IHC)] and on HER2 status (positive if IHC3+ and/or FISH amplified), both primary tumor and bone metastases were collected. Fisher and McNemar's test were used for statistical analysis. Results: Median time from primary diagnosis to bone biopsy was 4.2 years (range 0-18.9). Overall discordance rate (ODR) in ER expression was 20.5% (95% CI: 13.4%-29.5%): 3/7 pts (42.9%) shifted from ER negative to positive and 19/100 pts (19%) from ER positive to negative [p=0.0006]. ODR in PgR expression was 43.9% (95% CI: 34.3%-53.8%): 4/21 pts (19%) changed from PgR negative to positive and 43/86 pts (50%) from PgR positive to negative [P Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-13-03.

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.

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

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

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

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

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

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

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.

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

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.

La Societe internationale d’oncologie geriatrique (SIOG) cherche a promouvoir dans le monde entier une prise en charge du patient âge basee sur des considerations scientifiques. Afin de developper les approaches therapeutiques d’une facon coherente, il importe de savoir comment l’oncologie geriatrique est organisee dans les differents centres qui collaborent dans le cadre de la SIOG. Un total de 58 questionnaires ont ete completes, permettant de mettre en evidence qu’une evaluation geriatrique complete est pratiquee dans 60 % des centres, que 21 centres ont des programmes specifiques d’oncologie geriatrique, pour la plupart dans les departements de cancerologie. Soixante pour cent des centres ayant repondu indiquent que les patients de plus de 70 ans devraient pouvoir participer a des etudes cliniques, mais en realite seulement 20 % des centres y incluent des patients.

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

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

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

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.

Background: Oxaliplatin (OXA) significantly enhanced the antitumour activity of 5-fluorouracil (FUra) in patients with advanced colorectal cancer and displayed radiosensitising properties in preclinical studies. This study was thus performed to test the feasibility, identify the recommended doses (RDs) and explore preliminarily the clinical activity of weekly OXA and infused FUra combined with preoperative pelvic radiotherapy. Patients and methods: Forty-six patients with recurrent or locally advanced (cT3-4 and/or N+) adenocarcinomas of the mid-low rectum were treated with escalating doses of OXA (25, 35, 45, 60 mg/m2, weekly for 6 weeks) and FUra (200–225 mg/m2/day, 6-week infusion) concurrent to preoperative pelvic radiotherapy (50.4 Gy/28 fractions). The RDs for the phase II part of the study were immediately below the level resulting in dose-limiting toxicities in more than one third of the patients, or corresponded to the last planned dose level. Results: In the escalation phase, dose-limiting toxicities only occurred in one patient at the fourth level and one of six patients treated at the last planned dose level (grade III diarrhoea). OXA 60 mg/m2 and FUra 225 mg/m2/day are therefore the RDs for the regimen. Among 25 patients globally treated at these doses (phase II part), the incidence of grade III diarrhoea was 16% with no grade IV toxicity. Neurotoxicity did not exceed grade II (12%). All patients completed radiotherapy and were operated on as scheduled. Twenty-one of 25 patients had the tumour down-staged after chemoradiation with seven (28%) pathological complete responses and 12 (48%) residual tumours limited to ypT1-2N0. Conclusions: Weekly OXA, at doses potentially active systemically, can be combined with full-dose, infused FUra and radiotherapy. Given the low toxicity and promising activity, this regimen is being compared to standard FUra-based pelvic chemoradiation in a randomised study.

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.

http://hdl.handle.net/20.500.11768/96435