Systemic recurrence of endometrial cancer more than 10 years after hysterectomy: a report of two cases and a brief review of the literature.

BACKGROUND: Endometrial carcinoma is one of the most common female cancers in developed countries. Disease stage is associated with the risk of disease relapse after radical treatment. Typically, the risk of disease relapse peaks at 3 years from local radical treatment and then diminishes over time, so that late relapses (i.e., from year 5 afterward) are extremely infrequent. Here, we report two cases of women with endometrial cancer who developed a disease relapse more than 15 years after radical treatment. A review of the literature revealed other seven reports of women with relapse from endometrial cancer occurring more than 10 years after radical treatment. CASE PRESENTATION: Case report 1 is a 56-year-old woman with an endometrioid cancer who underwent a hysterectomy with bilateral salpingo-oophorectomy in 1998. She relapsed in the lung in 2014, 16 years from radical surgery. Case report 2, a 75-year-old woman, with an endometrioid cancer, was treated by hysterectomy with bilateral salpingo-oophorectomy and adjuvant radiotherapy. The disease relapse in the lung was detected in 2019, 22 years from radical treatment. CONCLUSION: Although guidelines do not support oncological follow-up beyond 5 years from surgery, oncologists should consider late recurrence of endometrial carcinoma in the differential diagnosis of women presenting with metastases of uncertain origin and prior history of this disease.

Long-term disease control in a metastatic squamous cell carcinoma of the oral cavity treated with maintenance metronomic capecitabine.

Recurrent or metastatic disease occurs in two-thirds of head and neck squamous cell carcinomas and it is associated with poor prognosis. Systemic treatment with platinum-based chemotherapy in combination with the epidermal growth factor receptor-targeting monoclonal antibody cetuximab represents a preferred option for these patients. Upon the achievement of tumor response by combined treatment, maintenance with single-agent cetuximab is usually administered with the aim of prolonging disease control at the price of reasonable toxicity. Although rarely, however, cetuximab needs to be discontinued in the absence of disease progression because of intolerable side effects. Here we describe the case of a 66-year-old man with a metastatic cancer of oral cavity, who had to discontinue maintenance cetuximab and who achieved prolonged disease control with metronomic capecitabine. We suggest that capecitabine could be an effective and safe maintenance option in case of cetuximab intolerance.

Variation in gynecological oncology follow-up practice: attributable to cancer centers or to patient characteristics? A Piedmont Regional Oncology Network Study.

AIMS AND BACKGROUND: Although guidelines recommend minimalist follow-up, there is wide variability in gynecological oncology practice. The aims of this study were to describe between-center differences in the follow-up of endometrial, ovarian, and uterine cervical cancer; to identify the determinants of test prescription; to estimate the related costs; and to assess the weight of center habits and patient characteristics as sources of unexplained variability. METHODS AND STUDY DESIGN: The medical records of patients treated between August 2004 and July 2005 for gynecological malignancies and followed up for the detection of recurrent disease were retrospectively collected from 29 centers of the Piedmont Oncology Network. Multivariate multilevel analyses were performed to study the determinants of test prescription and costs. RESULTS: Analyses were performed on 351 patients (median follow-up: 578 days). The unexplained variability in computed tomography prescriptions (26%), ultrasound prescriptions (17%), and total cost of follow-up (15%) can be attributed to center habits, independenty of the clinical characteristics of the patients. CONCLUSIONS: Much of the unexplained variability in the follow-up for gynecological malignancies is attributable to different habits of centers belonging to a cancer network. These results prompted us to design a multicenter randomized controlled trial to compare minimalist versus intensive follow-up programs in endometrial cancer.

Restless legs syndrome and its relationship with anxiety, depression, and quality of life in cancer patients undergoing chemotherapy.

OBJECTIVE: Restless legs syndrome (RLS) is a common sensorimotor disorder characterized by uncomfortable and unpleasant sensations in the legs that are relieved by movement. This study evaluated the prevalence of RLS in a consecutive series of cancer patients during chemotherapy and examined the relationship between presence of RLS and quality of life, anxiety, and depressive symptoms in these patients. METHODS: RLS was assessed according to the International RLS Study Group essential diagnostic criteria in two stages: a screening questionnaire first, followed by a sleep specialist-conducted structured diagnostic interview. The following questionnaires were administered: Functional Assessment of Cancer Therapy-General (FACT-G) for Quality-of-life (QoL) assessment; Hospital Anxiety and Depression Scale (HADS) to evaluate the levels of anxiety and depression; and Mini Mental Adjustment to Cancer Scale (Mini-MAC) to assess coping styles. RESULTS: A total of 257 patients were evaluated. Among them 56 were identified by the screening questionnaire to meet the criteria for RLS and 47 of whom were confirmed as affected by RLS after a structured interview, rendering a prevalence rate of 18.3%. RLS was significantly more frequent in women than men (23.7 vs. 11.8%; P = 0.01), and in patients receiving antineoplastic therapies for more than 3 months than their counterpart (21.8 vs. 10.8%; P = 0.03). Compared with those without RLS, patients with RLS had higher levels of anxiety (P = 0.0009) and depression (P = 0.001) and lower quality of life (P = 0.006). Sex-chemotherapy-duration-adjusted odds ratios of anxiety and physical well-being associated with RLS were 1.1 (95% CI 1.00-1.19; P = 0.04) and 0.7 (95% CI 0.43-1.01; P = 0.04), respectively. CONCLUSIONS: The prevalence of RLS in cancer patients undergoing chemotherapy is 18.3%, about double of that expected in the general population. The occurrence of RLS is much more frequent in female patients and with longer-term chemotherapy. Cancer patients afflicted by RLS have significantly higher levels of anxiety and depression, and poorer quality of life especially in the physical well-being dimension. Recognition and treatment of RLS in cancer patients is an important target in clinical management and may improve quality of life and overall health outcomes in these patients.

Gemcitabine and protracted 5-fluorouracil infusion as third-line chemotherapy in refractory colorectal cancer patients.

BACKGROUND: There is no standard treatment for patients with advanced colorectal cancer (CRC) progressing after irinotecan and oxaliplatin treatment and having good performance status (PS). PATIENTS AND METHODS: We investigated gemcitabine 1,000 mg/m2 days 1, 8 and 15 q28d combined with protracted 5-fluorouracil continuous infusion at 200 mg/m2/day, in 37 consecutive patients progressing after oxaliplatin-irinotecan-containing chemotherapies. RESULTS: Partial response (PR) was achieved in 4 (10.8%) and disease stabilization (SD) in 19 (51.4%) cases (PR+SD: 62.2%). Median time to progression and survival were 4.2 and 8.9 months, respectively. Grade III toxicities were thrombocytopenia, neutropenia (in 3 patients) and mucositis (in 2 patients). Clinical benefit was observed in 18 patients (48.6% of the entire population; 64.3% of those patients with PS>0 at study entry). CONCLUSION: The combination of gemcitabine and 5-fluorouracil continuous infusion was found to be an active and manageable palliative regimen for heavily pre-treated patients with metastatic CRC.

Development and validation of a patient-physician relationship index in the advanced cancer setting.

BACKGROUND: The quality of the relationship between patient and medical staff is crucial in oncological settings. We have developed and validated a short, self-administered questionnaire to measure patients' satisfaction with their relationship with the physician: the Patient-Physician Relationship Index (PPRI). MATERIALS AND METHODS: Content validity was evaluated by a two-stage (development and judgment) process. One hundred and nine cancer patients with metastatic disease were assessed during the second cycle of chemotherapy and 59 were reassessed eight weeks later. Quality of life and anxiety and depression were also evaluated. RESULTS: The PPRI is monofactorial. Cronbach's alpha coefficient was 0.81. Sensitivity to change was shown by the correlation with changes in patients' conditions. The PPRI scores were only weakly correlated with the majority of the EORTC and HAD subscale scores. CONCLUSION: The PPRI is an easy-to-use, self-administered questionnaire, developed in a population of patients with advanced cancer. It has good internal consistency and sensitivity to change.

Prognostic significance of changes in CA 15-3 serum levels during chemotherapy in metastatic breast cancer patients.

Tumor response to first-line chemotherapy in advanced breast cancer offers prognostic information and may be used as a surrogate marker for evaluating treatment efficacy. With this study we wanted to determine whether changes in circulating serum CA 15-3 levels during chemotherapy provided additional information for prognostic prediction. Serum CA 15-3 was measured at baseline and after 3 and 6 months during anthracycline-based first-line chemotherapy in 526 patients with advanced breast cancer prospectively enrolled in five phase II-III trials. Changes in marker levels were correlated with disease response, time to progression and overall survival. In all, 336 patients attained a disease response. A significant relationship was found between disease response and CA 15-3 variations, although many individual discrepancies were also observed. At the 6-month time point, the median time to progression was 15.3 months in patients with normal marker levels throughout the study, 11.7 months in those with a CA15-3 reduction >25%, 9.6 months in those with elevated baseline CA 15-3 levels which did not change during therapy and 8.6 months in those with increased marker levels (p < 0.001). The median survival was 42.3, 29.7, 28.5, and 24.8 months, respectively (p < 0.002). The prognostic role of changes in CA 15-3 levels was maintained in the patient subset attaining disease response or stabilization to treatment (p < 0.001) and after adjusting for clinical response and major prognostic parameters in the multivariate analysis (p < 0.001). In conclusion, monitoring serum CA 15-3 levels during first-line chemotherapy in advanced breast cancer patients provides prognostic information independently from tumor response.

Feasibility of 21-day continuous infusion of epirubicin in hormone-refractory prostate cancer patients.

BACKGROUND: Epirubicin (EPX) has been found to be active in hormone-refractory prostate cancer (HRPC) patients. Prolonged EPX infusion has never been investigated in this patient subset. PATIENTS AND METHODS: A feasibility study was conducted in which EPX was administered in 21-day continuous infusion to 15 patients with HRPC. The EPX dose was 5 mg/m2 daily for 21 consecutive days (one course). One week was allowed before starting the next course. RESULTS: The patients received 1 to 6 courses (median 3). As a whole, the treatment was well tolerated. Nine patients did not develop any toxicity, while WHO grade 3 and 4 toxicities were recorded in 4 patients. Alopecia (WHO grade 1-2) was presented in 4 cases. Five patients attained >50% decrease in serum prostate-specific antigen (PSA). CONCLUSION: Prolonged EPX infusion is feasible and potentially active in the treatment of HRPC patients. Our data suggest caution in administering this treatment in patients bearing rheumatologic disease.

Oral estramustine plus oral etoposide in the treatment of hormone refractory prostate cancer patients: a phase II study with a 5-year follow-up.

BACKGROUND: Chemotherapy regimens that target microtubular trafficking were repeatedly found to be active in the treatment of hormone refractory prostate cancer patients, but disease responses were reportedly short-lived on average. MATERIALS AND METHODS: From 1994 to 1997, 46 consecutive patients with hormone refractory prostate cancer were enrolled in a multicenter Phase II trial of oral etoposide 100 mg/day and estramustine 560 mg/day for 21 days, followed by a 7-day rest period. Final evaluation of this trial was performed after a follow-up of 5 years. RESULTS: Fifty-four percent of patients attained a PSA response and 46% attained a response on measurable lesions. Median time to progression (TTP) and overall survival were 7.4 and 18.4 months, respectively. Fourteen patients (30.4%) had a TTP greater than 12 months and 9 (19.5%) a TTP greater than 18 months. Sixteen patients (34.8.%) survived more than 2 years and 2 (4.3%) survived more than 5 years. One patient was still alive and free from progression more than 7 years after starting treatment. CONCLUSIONS: This Phase II trial with a long-term follow-up revealed that some patients with hormone refractory prostate cancer could obtain durable disease response and long survival with an oral etoposide and estramustine combination regimen.

Background to and management of treatment-related bone loss in prostate cancer.

Prostate cancer is a common disease among older men. Androgen suppression by either orchiectomy or administration of luteinising hormone-releasing hormone (LHRH) analogues is the mainstay of treatment. Since the use of prostate-specific antigen (PSA) serum testing has become widespread, however, the timing of endocrine therapy has expanded considerably to include patients with limited involvement of extraprostatic sites and patients presenting an isolated elevation of PSA after radical treatments. These patients are expected to be treated for a long time, since they have a rather low risk of disease progression and there is no recommended time limit for LHRH analogue therapy. The long-term adverse effects of androgen deprivation therapy, therefore, deserve more attention than they have received in the past. Osteoporosis represents a special concern for men with prostate cancer receiving androgen deprivation therapy. The rate of bone loss in these men seems to markedly exceed that associated with menopause in women, and fractures occur more frequently than in the healthy elderly male population. Serial bone mineral density (BMD) evaluation could allow the detection of patients with prostate cancer who are at greater risk of osteoporosis and adverse skeletal events after androgen deprivation therapy, such as patients already osteopenic or osteoporotic at baseline and men with rapid bone loss during treatment. BMD evaluated during treatment could also be a potential surrogate parameter of antiosteoporotic therapeutic efficacy. Treatment of bone loss induced by androgen deprivation comprises general prevention measures, antiosteoporotic drugs and the use of alternative endocrine therapies. Optimising lifestyle and diet is important, although it cannot completely prevent bone loss. Patients with nonsevere bone disease may benefit from calcium and vitamin D supplements. Men who are osteoporotic before androgen deprivation or men becoming osteoporotic during treatment and/or experiencing adverse skeletal events may also require bisphosphonates. The effectiveness of these drugs in preventing fractures has been shown in a single randomised study involving patients with osteoporosis, but it has not yet been established in a prostatic cancer population without bone metastases given androgen deprivation therapy. Different forms of endocrine therapy such as low-dose estrogens, antiandrogens and intermittent androgen ablation are under investigation. They could offer the advantage of avoiding (or limiting) treatment-related bone loss. In our opinion, however, the data available so far are not robust enough to recommend these alternative endocrine therapies instead of standard androgen deprivation in routine clinical practice.

Time to progression in metastatic breast cancer patients treated with epirubicin is not improved by the addition of either cisplatin or lonidamine: final results of a phase III study with a factorial design.

PURPOSE: To investigate the value of the addition of either cisplatin (CDDP) or lonidamine (LND) to epirubicin (EPI) in the first-line treatment of advanced breast cancer. PATIENTS AND METHODS: Three hundred seventy-one metastatic breast cancer patients with no prior systemic chemotherapy for advanced disease were randomized to receive either EPI alone (60 mg/m(2) on days 1 and 2 every 21 days), EPI and CDDP (30 mg/m(2) on days 1 and 2 every 21 days), EPI and LND (450 mg orally daily, given continuously), or EPI, CDDP, and LND. Time to progression, response rates, side effects, and survival were compared according to the 2 x 2 factorial design of this study. RESULTS: The groups were well balanced with respect to prognostic factors. Time to progression did not differ in the comparison between CDDP arms and non-CDDP arms (median, 10.9 months v 9.4 months, respectively; P =.10) or between that of LND arms and non-LND arms (median, 10.8 months v 9.9 months, respectively; P =.47), nor did overall survival. The response rate did not significantly differ in the comparison between LND arms and non-LND arms (62.9% v 54.0%, P =.08). No difference in treatment activity was observed between CDDP arms and non-CDDP arms. Toxicity was significantly higher in the CDDP arms, leading to CDDP dose adjustment in 40% of cases. The most frequent side effects were of a hematologic and gastrointestinal nature. The addition of LND produced more myalgias and fatigue. CONCLUSION: Neither CDDP nor LND was able to significantly improve the time to progression obtained by EPI. CDDP, however, significantly worsened the drug's tolerability.