Annalisa Giacalone

Modulated Chemotherapy According to Modified Comprehensive Geriatric Assessment in 100 Consecutive Elderly Patients with Diffuse Large B-Cell Lymphoma

Chemotherapy is associated with toxicity in elderly patients with potentially curable malignancies, posing the dilemma of whether to intensify therapy, thereby improving the cure rate, or de-escalate therapy, thereby reducing toxicity, with consequent risks for under- or overtreatment. Adequate tools to define doses and combinations have not been identified for lymphoma patients. We conducted a prospective trial aimed to evaluate the feasibility and efficacy of chemotherapy modulated according to a modified comprehensive geriatric assessment (CGA) in elderly (aged ≥70 years) patients with diffuse large B-cell lymphoma (DLBCL). In June 2000 to March 2006, 100 patients were stratified using a CGA into three groups (fit, unfit, and frail), and they received a rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone modulated in dose and drugs according to comorbidities and activities of daily living (ADL) and instrumental ADL scores. Treatment was associated with a complete response rate of 81% and mild toxicity: grade 4 neutropenia in 14%, anemia in 1%, and neurological and cardiac toxicity in 2% of patients. At a median follow-up of 64 months, 51 patients were alive, with 5-year disease-free, overall, and cause-specific survival rates of 80%, 60%, and 74%, respectively. Chemoimmunotherapy adjustments based on a CGA are associated with manageable toxicity and excellent outcomes in elderly patients with DLBCL. Wide use of this CGA-driven treatment may result in better cure rates, especially in fit and unfit patients.

The Revised Piper Fatigue Scale (PFS-R) for Italian cancer patients: a validation study

BACKGROUND AND AIM Fatigue is one of the most frequently reported symptoms by cancer patients. In recent years, much effort has been directed to designing fatigue measures which are psychometrically appropriate as well as easily administered. Among these, the Revised Piper Fatigue Scale (PFS-R) is widely used in assessing fatigue in cancer patients and other populations. Despite its large utilization in different national contexts and with different populations, its structure appears to vary across cultures, suggesting the need for its validation before use. The main aim of the present work was to verify the validity (i.e., dimensional structure and construct validity) and reliability (i.e., internal consistency) of an Italian translation of the PFS-R to reassure Italian oncology practitioners about its appropriate usage in practice and research. METHODS AND STUDY DESIGN One-hundred ten Italian oncological inpatients were administered an Italian translation of the PFS-R together with a form for the collection of personal identification and clinical data and other fatigue and quality of life measures (POMS and EORTC QLQ-C30) already validated for Italy. RESULTS Principal component exploratory factor analysis revealed a four-factor structure quite similar to (although not overlapping) the original described by Piper and colleagues; all four factors proved to be reliable and to correlate with one another and with previous validated measures of fatigue and quality of life. Preliminary descriptive statistics were also provided for data comparisons. CONCLUSIONS Despite the discussed limitations, PFS-R seems a valid and reliable multidimensional fatigue measure also adequate in Italian oncological settings.

Small cell lung cancer in an elderly patient: efficacy of somatostatin analog treatment, a case report.

enolase (NSE), the group of chromogranins, and synaptophysin; when proteins are released into the blood, they can result in a clinically functioning neuroendocrine syndrome [5]. It has been demonstrated by in vitro studies that NETs of the lung can overexpress several peptide receptors: somatostatin receptors (SSTRs) are the most common, although other peptides have been reported less frequently, such as vasoactive intestinal peptide (VIP), cholecystokinin (CCK), neurotensin, bombesin/gastrin-releasing peptide, atrial natriuretic peptide (ANP), calcitonin and calcitonin gene-related peptide (CGRP), oxytocin, and glucagon-like peptide-1 [6]; these findings have been confirmed in vivo by Octreoscan evaluation and immunohistochemistry [7]. In the chest, besides in NETs, SSTR have also been demonstrated in granulomatous diseases, like sarcoidosis and other immune-mediated disorders such as anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis [8]. Their expression was occasionally demonstrated in non-small cell lung cancer (NSCLC) [9]. The activity of somatostatin (SS) is due to its interaction with a family of transmembrane receptors, the SSTR family, including 5 different G-protein-coupled receptors (from SSTR1 to SSTR5). Recently, several peptides like octreotide or lanreotide have been discovered, with similar binding affinity as SS to its receptors and similar activity [10]. Those derivatives of somatostatin are effective in the secretory regulation of NET cells; however, they have been disappointing as antiproliferative agents in vivo for gastrointestinal carcinoids [11]; in contrast, in vitro experiments have shown effective inhibition of cell proliferation in lung NETs by somatostatin analogs [12], although there are only few and non-conclusive clinical reports [13, 14]. Another clinical use of SS analogs is related to the possibility of visualizing SSTRpositive tumors and mapping their localizations by injecting labeled peptides [15].

Is Long-Term Fatigue in Patients With Cancer an Infrequent Symptom?

TO THE EDITOR: The prospective study by Goldstein et al addresses an interesting ongoing and unresolved debate regarding the effects and prevalence of cancer-related fatigue (CRF) in patients with cancer. In a cohort of women who received adjuvant treatment for early-stage breast cancer, the authors showed that CRF was a common symptom but generally ran a self-limiting course. However, some concerns might affect the generalizability of their findings. First, the reasons for exclusion from the study of 118 patients (84 patients at the time of enrollment and 34 patients after 12 months) were not described. It is possible that, among these patients, some women were too fatigued to accept being enrolled or continuing on and completing the questionnaires. In theory, this effect could explain the surprisingly low numbers of patients who suffered from CRF 1 year after the end of treatment (18 of 218 patients) and 5 years after the end of treatment (26 of 218 patients). In addition, it would be interesting to know whether fatigue was also present before treatment started (ie, were enrolled patients fatigued weeks, months, or years before the diagnosis of cancer?). In other words, it could useful to differentiate patients with fatigue closely related to cancer and/or a cancer diagnosis from patients affected by chronic fatigue and breast cancer. Moreover, the article considered only women with breast cancer. It would be interesting to compare this cohort of patients with both male and female fatigued patients affected by other malignancies like lymphomas. On the basis of these considerations, we question the generalizability of the study by Goldstein et al. If the data were available, we hypothesize that the presence and course of fatigue in this population of patients with cancer could have been underestimated within the study. Additional research is needed on this topic to better define the fatigue experienced by patients with cancer.

Symptom burden in cancer survivors 1 year after diagnosis: a report from the American Cancer Society's Studies of Cancer Survivors.

We read with interest the article by Shi et al in which 1 in 4 cancer survivors defined as patients within 1 year of diagnosis and on treatment showed high symptom burden, with fatigue being the main symptom and having the greatest impact on health-related quality of life. We believe that cancer survivors should be defined as patients without evidence of disease and free from specific treatment for a period of at least 5 years. In fact, it is conceivable that patients with active disease and/or on treatment may suffer from the fatigue associated with cancer and its treatments as well as other related causes, including anemia, endocrine and metabolic disorders, and cardiovascular and renal dysfunction (i.e., cancerrelated fatigue). On the contrary, in long-term cancer survivors, fatigue has been described as a chronic/persistent condition associated with disrupting symptoms similar to chronic fatigue syndrome (CFS). In fact, in these cancer patients, fatigue may appear years after the cancer diagnosis and the end of treatment. Fatigue is usually associated with postexertional malaise; sore throat; tender cervical or axillary lymph nodes; muscle pain; multijoint pain without joint swelling or redness; headaches of a new type for pattern or severity; unrefreshed sleep; and self-reported impairment of short-term memory or concentration severe enough to have a substantial impact on a patient’s occupation, education, or personal activities. For these reasons, we believe that fatigue in long-term cancer survivors must be considered a subtype of CFS, and that it could be defined as CFS/cancer-related fatigue. In conclusion, we believe that in cancer patients, there are 2 kinds of fatigue that require different symptom monitoring and management: one is observed during therapy and should thus be defined as cancer-related fatigue, whereas the other is observed after therapy and thus could be defined CFS/cancer-related fatigue. Further studies should be performed in these settings to better define these 2 entities. CONFLICT OF INTEREST DISCLOSURES The authors made no disclosures.

Perceptions and attitudes of clinical oncologists on complementary and alternative medicine: a nationwide survey in Japan.

In their survey, Hyodo et al. concluded that negative perceptions regarding complementary and alternative medicine (CAM) products persist among clinical oncologists in Japan. On behalf of the Italian National Institute of Health, a project concerning CAM was initiated in Italy. As part of this project, we designed a survey to investigate the use of CAM by cancer patients based on previous surveys. 4 Between May 2001 and August 2002, 426 cancer inpatients who were admitted to 4 institutions located in different areas of Italy were asked to answer a 30-question, self-administered survey concerning the use of CAM for their neoplasia. Approximately 10% of the patients declared that they had used CAM remedies for their cancer. The remedies used most often were herbal and botanical treatments, homeopathy, dietary regimens, and energy healing. The main reasons for using CAM were concern for the adverse effects of conventional anticancer treatments, to increase the patient’s well-being, and to increase the chance of cure. Factors demonstrating statistical significance for CAM use were female gender, residency in northern Italy, duration of the cancer of 12 months, and previous multiple conventional anticancer treatments. Age, education, marital status, profession, and type of cancer did not appear to influence the decision to use CAM. The preferential choice of herbal and botanical treatments may be explained by the constant bombardment by mass media, prompting the return to a more “natural” lifestyle. We believe CAM remedies are viewed by cancer patients as more of a support with which to better cope with conventional oncologic treatments rather than as an alternative to these treatments. It is worthwhile to note that 63% of the patients declared that they had not informed their treating oncologist about their use of CAM and in only 52% of the cases had CAM been prescribed by a physician. We are aware that a thorough reflection on the physician-patient relationship is needed. Even if 383 patients declared that they had never used CAM for their neoplasia, 66% of the sample patients wished for an interaction between conventional treatments and CAM. The belief that conventional anticancer treatments bear an intense level of physical and psychologic suffering still is deeply rooted. Therefore, patients often are desperately seeking help to minimize their suffering. In this setting, we agree with Hyodo et al. when they state that strategic efforts are needed to provide guidance for patients so that they may better interpret the medical information. Given the lack of proven effectiveness of CAM treatments, oncologists need to be aware of the magnitude of this problem. 2302

Non-Hodgkin's lymphoma (NHL) in elderly patients (pts): Patient-tailored treatment according to a comprehensive geriatric evaluation

6678 Background: Elderly patients affected by aggressive NHL are generally not treated in an optimal way. Therefore, we designed a new approach for elderly pts (>70 years) with aggressive NHL, that allows a pt-tailored treatment with the aim of maintaining a balance between the desire of curing the tumor and the need of providing a good quality of life. METHODS The study was started in March 2000. Pts with an ADL and IADL score of at least 5 and whose hepatic and renal function and hemopoietic reserve are sufficiently good, are treated with curative intent. These pts receive CHOP (those with a very good functional status) or CEOP (if mild cardiopathy is present) or CVP (if severe cardiopathy is present) or CEO (if diabetes mellitus is present). Dose reductions of chemotherapy (CT) are also applied according to IADL and ADL. Rituximab is administered if CD20+; G-CSF is administered from day 7 to 12. RESULTS So far, 61 pts have been enrolled. Median age was 75 years (range: 70-89). Fifty patients are evaluable for response (see table). Hematologic toxicity was evaluated in 42 patients (173 cycles) and G3-G4 toxicity at nadir was registered in 16 cycles (9.2%). Non-hematologic toxicity was evaluated in 56 patients (239 cycles) and was as follows: G3 gastrointestinal in 2 cycles, G3 neurologic in 9 cycles, G3 infection in 4 cycles. Median follow up is 13 months (range 1-43). Five pts relapsed. Thirty-four patients are still in CR. Nine patients died (2 early deaths, 6 PD and 1 respiratory failure in CR one month after the end of CT). CONCLUSIONS Our results demonstrate that this completely new approach is feasible for elderly pts with NHL. We strongly believe that it is highly effective and without significant toxicity. We also believe that a similar approach should be employed for future studies aimed at determining the best treatment for elderly pts affected by any cancer type. [Figure: see text] No significant financial relationships to disclose.