General Performance Status Research Articles

Hepatic Resection for Extrahepatic Metastatic Disease: When Is It Reasonable?

The presence of limited and resectable extrahepatic metastases (EHM) in addition to colorectal liver metastases (LM) is no longer a contraindication to surgery. Long-term survival (between 25 and 30 % at 5 years) is possible for highly selected patients. The site of occurrence is a key prognostic factor. Results are best for lung EHM and limited peritoneal metastases (PM), lower when EHM invade the proximal hepatic lymph nodes, and worse for other EHM. Treatment decision making is difficult when faced with an infinite number of possible combinations between the different sites of metastases, their number, and the overall tumor load. General performance status, technical contingency, and chemosensitivity are also important factors to be reckoned with. In the future, a considerable amount of data concerning these patients and new statistical tools will be required to create clear decision trees.

Behavioral risk factors of constipation in palliative care patients.

BackgroundConstipation is frequently encountered in palliative care patients and remains a significant therapeutic problem. The etiology of constipation is multifactorial. Nutritional and behavioral factors are considered common causes of constipation; however, their impact has not yet been assessed precisely.ObjectiveThe aim of this study was to assess the correlation between the frequency of bowel movements (FoBM) and risk factors of constipation in palliative care patients.Design and subjectsA cohort retrospective study was performed in three palliative care centers, including outpatient, home, and inpatient care cancer patients using questionnaires on bowel dysfunction symptoms, behavioral risk factors, and opioid use. The inclusion criterion was adult patients examined on the day of admission. The exclusion criterion was Karnofsky performance status score ≤20.MeasurementsSpearman’s rank correlation coefficient was used to measure the statistical dependence between two variables and frequency analysis was performed using the chi-squared test and Fisher’s exact test.ResultsTwo hundred thirty-seven valid questionnaires were collected. We found the correlation between FoBM and insufficient food and fluid intake (p < 0.0001), as well as for inadequate conditions of privacy (p = 0.0008), dependency on a caregiver (p = 0.0059), and the patient’s overall performance status (p = 0.013). We did not manage to prove bed rest as the independent risk factor of constipation.ConclusionsThe main risk factors of constipation in palliative care patients appeared to be insufficient fluid and food intake, inadequate conditions of privacy, dependency on a caregiver, as well as poor general performance status.

Advanced POEMS syndrome treated with high-dose melphalan followed by autologous blood stem cell transplantation: a single-center experience.

BackgroundPOEMS syndrome is a rare paraneoplastic syndrome associated with plasma cell dyscrasia. High-dose chemotherapy followed by autologous stem cell transplantation has shown encouraging efficacy in the treatment of patients with POEMS syndrome. However, there are minimal reports on clinical outcomes after autologous stem cell transplantation for patients with advanced disease and very poor performance status.MethodsWe retrospectively evaluated 9 advanced POEMS syndrome patients, who had an Eastern Cooperative Oncology Group performance status score of 3 or 4, and were treated with high-dose melphalan therapy followed by autologous stem cell transplantation from 2004 to 2011.ResultsEight patients achieved initial hematologic response, 4 of whom had complete responses. At a median follow-up of 44 months (range, 8-94 months), 7 patients were alive, with 3-year overall survival rate of 77.8%. There were no hematologic relapses in the survivors. One patient died of disease progression; the other died of pneumonia despite a hematologic response 3 months after autologous stem cell transplantation. All survivors achieved improvement in general performance status and in clinical response.ConclusionHigh-dose melphalan followed by autologous stem cell transplantation can be considered a valid treatment option even for patients with advanced POEMS syndrome.

Multimodale Therapie des Pankreaskarzinoms

Adenocarcinoma of the exocrine pancreas is one of the most aggressive types of solid tumor and stands at fourth position in the tumor death frequency scale due to a high mortality rate. Effective screening methods are not available and only radical surgery offers a curative option. With adjuvant chemotherapy the median survival time can be prolonged up to 23 months and approximately 25 % of patients are still alive after 5 years. Of these patients approximately 75-80 % are already in a palliative therapy situation at the time of diagnosis. In the last 5 years treatment options have been increased by the introduction of new chemotherapeutic drugs. For patients with metastasized disease median survival times of 6-12 months can currently be achieved depending on the general performance status at diagnosis but less than 5 % of these patients are still alive after 5 years. Neoadjuvant treatment strategies, radiation and immunotherapy do not play a role in evidence-based clinical practice. Despite progress in the understanding of cancer biology and new treatment options, non-resectable adenocarcinoma of the pancreas remains a disease with a very poor prognosis.

Management of "very early" hepatocellular carcinoma on cirrhotic patients.

Due to the advances in screening of cirrhotic patients, hepatocellular carcinoma (HCC) is being diagnosed in earlier stages. For this reason the number of patients diagnosed of very early HCC (single tumors ≤ 2 cm) is continuously increasing. Once a patient has been diagnosed with this condition, treatment strategies include liver resection, local therapies or liver transplantation. The decision on which therapy should the patient undergo depends on the general patients performance status and liver disease. Anyway, even in patients with similar conditions, the best treatment offer is debatable. In this review we analyze the state of the art on the management of very early HCC on cirrhotic patients to address the best treatment strategy for this patient population.

Ruxolitinib Before Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) In Patients With myelofibrosis : a Preliminary Descriptive Report Of The JAK ALLO Study, a Phase II Trial Sponsored By Goelams-FIM In Collaboration With The Sfgmtc

Ruxolitinib (RUXO) is a JAK inhibitor recently approved in France in patients (pts) with myelofibrosis (MF) because of its efficacy on splenomegaly and constitutional symptoms. Although no prospective safety data are available, many centers have started to use RUXO before HSCT to improve general performance status and decrease splenomegaly (influencing the engraftment).This academic study (ClinicalTrials.gov: NCT01795677) was designed to assess the impact of RUXO in pts with MF candidates for HSCT. Primary objective is the achievement of a disease-free survival at 1 year post HSCT > 50%. A total of 53 pts should be transplanted in order to reach this endpoint. Secondary objectives include: probability to be transplanted in pts with donor, overall survival, non-relapse mortality, hematological response, rate of pre-HSCT splenectomy, quality of life and MF-associated symptoms (through questionnaires). Inclusion criteria are: pts with MF, < 70 years, with either an intermediate or high risk MF according to Lille or IPSS score, or poor prognostic cytogenetics: complex karyotype, abnormalities of chromosomes 5, 7 or 17. Pts with platelets < 50 G/L, blasts ≥ 20% or previously treated with RUXO are excluded. After inclusion, RUXO is started at 15 mg BID in pts with platelets > 100 G/L or 10 mg BID in pts with platelets < 100 G/L and the search for a donor is started. If a donor is identified (related or unrelated HLA matched), the patient should be transplanted within 4 months. Pts without donors are prospectively followed on RUXO therapy in a parallel group. Conditioning regimen (CR) consists in melphalan and fludarabine, started after RUXO tapering and discontinuation. In May 2013, as some unexpected severe adverse events (SAE) were reported, investigators decided to stop enrollment of pts and to amend the protocol with new prophylactic measures.Twenty-three pts have been enrolled between Dec 2012 and May 2013 (1 pt excluded for inclusion criteria violation). Median age was 59 years (45-67). MF was primary in 19 and post essential thrombocytemia or polycythemia vera in 3 pts. All pts had splenomegaly (median: 23 cm). 12 pts had the JAK2V617F mutation. Cytogenetics were normal in 7, abnormal in 10 (poor prognostic in 2), missing or failed in 5 pts, respectively. Lille score was low in 5, intermediate (int) in 13 and high in 4 pts, resp. Age adjusted dynamic IPSS was low in 1, int-1 in 7, int-2 in 9, and high in 5 pts, respectively. Median follow-up was 149 days (69-229). Response after 2 months of RUXO was assessable in 16 pts: 50% partial remissions (- 25% in spleen size and improvement of constitutional symptoms) and 50% had stable disease. 8 pts have been transplanted (3 splenectomies before HSCT), 8 are waiting for HSCT, 4 pts have no donor identified yet and 2 pts were excluded from HSCT because of onset of comorbidities. Tolerance of RUXO was generally good and 3 SAEs were reported: febrile pancytopenia (n=2), multiple cranial nerve injury (n=1). The other SAEs (n=10) were reported within 21 days after RUXO discontinuation. Among the 10 pts who stopped RUXO, 7 had SAEs: multiple SAEs in 4, life-threatening in 7 and fatal in 2 pts, resp. Unexpected SAEs occurring after RUXO withdrawal included febrile cardiogenic shocks before HSCT not due to coronaropathy in 2 pts, and tumor lysis syndrome (TLS) with acute renal failure during CR in 1 pt. The 2 deaths were due to severe acute grade III-IV graft-versus-host disease refractory to steroids.The protocol was amended in May 2013 with TLS prophylaxis, modification of RUXO tapering with a shorter duration (10 days) systematically associated with steroids (0.5 mg/kg/day) and slight CR change (started with melphalan instead of ending). Despite this amendment, 2 other pts experienced TLS (but without renal failure) and 1 patient had a cardiogenic shock 9 days after HSCT. After review of the data with the Data Safety Monitoring Board, ethics committee and health authorities, the protocol is continued for the 22 pts already enrolled, but new inclusions are on hold until safety is confirmed.This preliminary report of the first prospective study assessing the impact of RUXO before HSCT in MF pts aims at highlighting unexpected SAEs, namely TLS (n=3) and cardiogenic shocks (n=3), that should be carefully considered in other prospective trials and clinical practice. According to the study design, all included pts should be transplanted before Oct 2013, and more information will be available for Dec 2013. Disclosures: Robin:NOVARTIS: gives ruxolitinib and a financial support for the JAK ALLO study Other. Kiladjian:Novartis, Celgene, AOP Orphan: Research Funding; Novartis, Sanofi, AOP Orphan: Honoraria; Novartis, Sanofi, AOP Orphan: Membership on an entity's Board of Directors or advisory committees.

CECOG experts’ recommendations on the use of denosumab in the prevention of skeletal-related events in bone metastases of lung cancer

Skeletal-related events represent a substantial burden for patients with advanced cancer. Randomized, controlled studies suggested superiority of denosumab over zoledronic acid in the prevention of skeletal-related events in metastatic cancer patients, with a favorable safety profile. Experts gathered at the 2012 Skeletal Care Academy in Istanbul to bring forward practical recommendations, based on current evidence, for the use of denosumab in patients with bone metastases of lung cancer. Based on current evidence, use of denosumab in lung cancer patients with confirmed bone metastases is recommended. It is important to note that clinical judgment should take into consideration the patient’s general performance status, overall prognosis, and live expectancy. Currently, the adverse event profile reported for denosumab includes hypocalcemia and infrequent occurrence of osteonecrosis of the jaw. Therefore, routine calcium and vitamin D supplementation, along with dental examination prior to denosumab initiation are recommended. There is no evidence for renal function impairment due to denosumab administration. At present, there is no rationale to discourage concomitant use of denosumab and surgery or radiotherapy.

The benefit of population-based studies for older patients with acute myeloid leukemia

The benefit of population-based studies for older patients with acute myeloid leukemia

A Homeopathic Approach to Treat Patients with Advanced Gallbladder, Periampullary, and Liver Carcinomas: A Report of 3 Cases

The authors present 3 cases of various pathologically confirmed malignancies (one gallbladder, one periampullary, and one liver). These patients underwent Psorinum therapy as the primary cancer treatment. Psorinum therapy is a homeopathic approach to treat patients with cancer. According to the American Joint Committee on Cancer tumor, nodes, metastasis system, all 3 patients were diagnosed at Stage IV. Their Karnofsky performance status was between 20% and 50% and their Eastern Cooperative Oncology Group score status was between 3 and 4. In these cases, conventional cancer treatments could not be initiated due to the advanced stage of their disease, poor general health performance status, and their financial constraints. In these patients, Psorinum-6x was administered orally at a dose of 0.02 mL/kg body weight/day on an empty stomach for a complete course duration of 2 years, along with allopathic and homeopathic supportive treatment. According to the Response Evaluation Criteria in Solid Tumors criteria, complete tumor response occurred in 1 case and partial tumor response occurred in the other 2 cases. All 3 patients remained alive and maintained a stable quality of life for at least 2 years. The patients reported no adverse side-effects from Psorinum-6x. This report indicates the clinical efficacy of Psorinum therapy in treating those 3 patients. Thorough basic research and well-designed clinical trials should be conducted for further investigation of this homeopathic cancer treatment in order to integrate it into the mainstream of oncology treatments.

Albumin Is a Prognostic Factor for Overall Survival in Newly Diagnosed Patients with Acute Myeloid Leukemia (AML)

Abstract 4253 Background:Hypoalbuminemia (HA) is a strong predictor of poor clinical outcomes in many medical conditions. Low serum albumin is recognized as an adverse prognostic factor in patients with neoplastic diseases such as multiple myeloma, melanoma, and colon cancer. Severe hypoalbuminemia (<3.0 g/dl) at day +90 post allogeneic hematopoietic cell transplant (AHCT) was reported as an independent predictive variable for non-relapse mortality and overall survival (Kharfan-Dabaja, et al Biol Blood Marrow Transplant 2009; 15). A separate study conducted by our group showed that in patients with relapsed and refractory AML, serum albumin < 3.5 g/dl prior to salvage chemotherapy, correlated with lower complete remission (CR) rate and inferior overall survival (OS) (Komrokji, et al ASH 2009). We examined the prognostic value of serum albumin level prior to induction chemotherapy in patients with newly diagnosed AML. Methods:Data were collected retrospectively in a cohort of newly diagnosed AML patients who received induction chemotherapy (3+ 7 regimen). The primary objective of this study is to examine the relationship between serum albumin at baseline and probability for achieving complete remission (CR) or incomplete remission (CRi) and overall survival (OS). All analyses were conducted using SPSS version 19.0. The Kaplan–Meier method was used to estimate median overall survival; chi-square test was used for comparison of categorical variables and t-test for continuous variables. Log rank test was used to compare Kaplan–Meier survival estimates between two groups and Cox regression for multivariable analysis. Results:Between November 2004 and July 2007, 135 patients who received 3+7 induction chemotherapy at Moffitt Cancer Center were included in this analysis. Patient baseline characteristics were similar between patients with baseline serum albumin < 3.5 g/dl (HA) and those with serum albumin ≥ 3.5 g/dl (no HA) with respect to age, sex, FAB subtype, history of antecedent MDS, karyotype, and chemotherapy. Patients with HA, mean age was 60 years compared to 56.5 years in non HA group.The median OS for patients with HA was 221 days (95%CI 149.5–292.5) compared to 421 days (95%CI 236.7–605) with normal serum albumin (p<0.005). (Figure-1) The CR/CRi rate was 64%% for HA and 77.6% for those with normal albumin (p=0.09). [Display omitted] In a multivariable Cox regression analysis including age ≥ 60 years, history of MDS, karyotype, and serum albumin level at baseline; only age, karyotype and serum albumin were independent predictors of OS [Hazard ratio 0.47 (95%CI 0.31–0.71) (p<0.005) for normal serum albumin group]. Conclusion:In this cohort of patients with newly diagnosed AML, we demonstrate that hypoalbuminemia < 3.5 g/dl is an independent covariate for overall survival with conventional chemotherapy management. Serum albumin is a surrogate marker of general health, comorbidities, and performance status. The prognostic value of low serum albumin should be validated in a prospective study. Disclosures:No relevant conflicts of interest to declare.

The impact of tumour histology and recursive partitioning analysis classification on the prognosis of patients treated with whole-brain hypofractionated radiotherapy for brain metastases: analysis of 382 patients

Recursive partitioning analysis (RPA) is a prognostic index capable of predicting survival in patients with brain metastases. Histology of the primary tumour has only recently been introduced among the factors that could potentially affect the prognosis of these patients. The main purpose of this study was to analyse the impact of RPA in correlation with histology of the primary tumour in patients with brain metastases treated with hypofractionated radiotherapy. A total of 382 patients were treated at the Department of Radiotherapy of Brescia University, and RPA classes were retrospectively assigned to all patients. Univariate and multivariate analyses were then performed to verify the role of the single prognostic variables, for the entire group and for each prognostic class, as well as in correlation with histology of the primary tumour. Most patients were classified as RPA prognostic class 2 (48%). The majority of patients was treated with a total dose of 30 Gy delivered in ten fractions, whereas the dose of 20 Gy in four or five fractions was primarily used in patients classified as RPA class 3. At univariate analysis, the main variable correlating with overall survival (OS) was RPA class (p=0.000). Uni- and multivariate analysis performed on RPA class 1 patients only confirmed the role of general performance status, number of metastases and total radiotherapy dose for predicting OS. In the group with the worst prognosis (RPA class 3), none of the variables had a statistically significant role in improving OS. Tumour histology and radiotherapy dose influence OS, even in RPA class 1 and 2 patients. This analysis confirms that RPA prognostic class is the factor that most predicts survival. Primary tumour histology helps determine prognosis, especially in RPA prognostic classes 1 and 2. As regards RPA class 3, no factor influences survival prognosis.

How I treat primary CNS lymphoma

AbstractPrimary CNS lymphoma (PCNSL) is a rare malignancy with peculiar clinical and biologic features, aggressive course, and unsatisfactory outcome. It represents a challenge for multidisciplinary clinicians and scientists as therapeutic progress is inhibited by several issues. Molecular and biologic knowledge is incomplete, limiting the identification of new therapeutic targets, and the particular microenvironment of this malignancy, and sanctuary sites where tumor cells grow undisturbed, strongly affects treatment efficacy. Moreover, active treatments are known to be associated with disabling neurotoxicity, posing the dilemma of whether to intensify therapy to improve the cure rate or to de-escalate treatment to avoid sequels. The execution of prospective trials is also difficult because of the rarity of the tumor and the impaired general condition and poor performance status of patients. Thus, level of evidence is low, with consequent uncertainties in therapeutic decisions and lack of consensus on primary endpoints for future trials. Despite this unfavorable background, laboratory and clinical researchers are coordinating efforts to develop new ideas, resulting in the recent publication of studies on PCNSL's biology and molecular mechanisms and of the first international randomized trials. Herein, these important contributions are analyzed to provide recommendations for everyday practice and the rationale for future trials.

Surgical results of patients after esophageal resection or extended gastrectomy for cancer of the esophagogastric junction

Precise classification of cancers of the esophagogastric junction according to Siewert may be difficult for the presence of Barrett's esophagus or hiatal hernia, which subsequently leads to a difficult choice of the surgical procedure of esophagectomy or gastrectomy. Ninety-six patients with such cancers were operated on in our department in 7 years. Twenty-nine patients (30.2%), classified as type I (group 1), underwent a transthoracic esophagectomy with gastric pull up. Sixty-seven patients (69.8%) classified as type II or III (group 2) underwent an extended gastrectomy. We compared the patients of both groups retrospectively for disease-free survival and postoperative complications. The general performance status of most patients was comparable in both groups and was assigned to the American Society of Anesthesiologists class II or III. Statistically significant differences between the groups were seen for the postoperative reintubation rate [group 1: 31.0% vs. group 2: 9.0% (P = 0.009)], median time for surgery [group 1: 6 (3.5-8.5) hours vs. group 2: 4.7 (2.2-11.5) hours (P = 0.001)], time in the intensive care unit [group 1: 6 (3-85) days vs. group 2: 3 (1-54) days (P = 0.001)], median hospitalization time [group 1: 23 (14-105) days vs. group 2: 18 (10-63) days (P = 0.018)]. No statistical difference was observed for the recurrence-free survival of 40% after 3 years (P = 0.311), the mortality rate, the morbidity rate (P = 0.108), surgical and respiratory complications, and the incidence of anastomotic leakage (P = 0.645). We conclude that in selected cases it may be possible to perform an extended gastrectomy for small type I cancers.

Efficacy of surgical resection in management of isolatedextrahepatic metastases of hepatocellular carcinoma

To clarify the benefit of surgical excision for patients with extrahepatic metastases of hepatocellular carcinoma (HCC). We retrospectively reviewed the medical records of 140 patients with pathologically proven extrahepatic metastases of HCC and evaluated the outcomes of those who had undergone surgical resection (SR) for extrahepatic metastatic lesions. Prognoses made on the basis of extrahepatic metastatic sites were also examined. The survival rates of patients who underwent SR of extrahepatic metastases were significantly better than those of patients who did not receive SR. For the SR group, 1- and 3-year survival rates were 24% and 7%, respectively, while for the non-resection group, the survival rates were 8% and 0%, respectively (P < 0.0001). Survival rates related to metastatic sites were also significantly superior after SR of extrahepatic metastases: median survivals were 32 mo with lung metastasis, 10 mo with bone metastasis, 6.1 mo with brain metastasis. SR can provide survival benefits for patients with 1 or 2 isolated extrahepatic metastases and who concurrently exhibit good hepatic functional reserve and general performance status as well as successful treatment of intrahepatic HCC.

Effects of Smoking Cessation on Hypoxia and its Potential Impact on Radiation Treatment Effects in Lung Cancer Patients

Smoking cessation is often attempted in the context of a lung cancer diagnosis. If cessation causes slowly continuing changes of total lung capacity and vital capacity, this may have consequences for lung volume, results of dose-volume histogram (DVH) analysis and targeting precision, in addition to changes in oxygenation, tumor biology (gene expression) and prognosis. To address the impact of smoking cessation on radiation treatment of lung cancer, a literature review was performed. Smoking cessation is associated with important benefits such as improved lung function and a better general health and performance status. In surgically and radiation treated patients, smoking cessation might lead to longer survival and reduced complications. Early data indicate that hypoxia in non-small cell lung cancer should be considered a poor prognostic factor. Yet, specific human data on how hypoxia is influenced by smoking status are not available. The influence of smoking history on the pneumonitis risk is not entirely clear. However, it appears that other factors outweigh the influence of smoking. The short-term effects of smoking cessation on lung function do not appear to cause relevant errors in treatment planning or targeting precision. Yet, no prospective study formally addressing this question was identified. Smoking cessation appears to be prognostically beneficial. The role of hypoxia in this context requires more detailed evaluation.

P3-054: Safety and efficacy of percutaneous cryosurgery under the ct guidance for the treatment of lung cancer

Many patients with lung cancer cannot undergo chemotherapy or radiation therapy due to impaired pulmonary function or poor general performance status. Most of them show resistance to these treatments, resulting in continued tumor growth and spreading. In such patients, minimally invasive treatments directed to local tumors may relieve patients from cancer pain or other generalized symptoms. As cryosurgery has been proven to be effective and also safe for cancers in prostate, kidneys, liver and endobronchial obstructive tumors, we sought to evaluate our results and safety of cryosurgery for lung cancer. At our hospital, from October, 2004 to December, 2005, 28 patients were treated by cryosurgery. The average age of the patients was 59.8. Of the 28 patients, 18 had primary lung cancer, and 10 had metastatic lung cancers. The average tumor size was 49.9mm. Cryosurgery was performed using a cryoprobe under CT guidance using local anesthesia. Follow up chest CT scan was taken at post operative day on 1 week, 1mo, 3mo and 6 months, and surgical final outcome was evaluated according to RECIST (complete remission, partial remission, stable disease, and progression). There were no procedure related mortalities. Postoperative pleural effusion was noted in 1 case (3.5%) and there were 9 cases (32%) of pneumothorax of which 3 needed closed thoracostomies. Small amounts of blood tinged sputum was noted by 15 of the patients (53.6%). Of the 28 patients, 3 patients (10.7%) showed complete remission and six (21.4%) resulted in disease progression. 21 patients (75%) of the patients exhibited response to the cryosurgical procedure. Cryosurgery for lung cancer can be performed safely under local anesthesia, and patients can be discharged early without serious complications. The effectiveness in local tumor destruction makes cryosurgery a promising option for the treatment of local tumors in patients with impaired pulmonary function, poor general performances, or those who refuse to take surgery

Long-Term Results of Free Radial Forearm Flap Used for Oral Reconstruction: Functional and Histological Evaluation

The aim of this study was to evaluate the radial forearm flap with regard to recovery of sensory function, general performance status, cutaneous blood flow and histological observations. Thirty patients (23 male and 7 female) with oral carcinoma underwent immediate reconstruction with radial forearm flap after ablative surgery and returned for evaluation. Interviews were conducted to assess the degree of articulation and mastication. Sensory function tests suggested the restoration of cutaneous sensibility of the forearm flap. Histological findings indicated mucosa-like changes of flaps about 10 months after reconstruction. The clarity of conversation recovered favorably in most patients. However, the degree of recovery was generally related to the time after surgery. The radial forearm flap is a unique flap with specific characters that allowed for best available functional reconstruction of the oral cavity in terms of restoration of sensation, performance, and histological changes to adapt to the new oral environment.

Long-term safety and efficacy of bisphosphonate (BP) therapy for more than 24 months (M) in breast cancer (BC) patients (pts) with bone metastasis (BM)

816 Background: In BC pts, bone is the most frequent site of distant metastasis. BPs exhibit highly beneficial effects on lytic bone lesions in BC pts. ASCO guidelines on the role of BPs in women with BC suggest that intravenous BPs be continued until evidence of substantial decline in general performance status (PS). However, the safety of continuing BP therapy for a prolonged period has rarely been investigated. We studied the long-term safety and efficacy of BP therapy in BC pts with BM who received BP therapy for more than 24 M as long-term administration. Methods: Pamidronate (PMT) 45mg and incadronate (INC) 10mg were given over 60 min intravenous infusion to BC pts with BM. The dosing interval was every 2 weeks at the start. When an effective response was obtained, BP was given at the interval of every 4 weeks or longer. PMT was given to all pts at the start, then changed to INC when there was no response. All pts received systemic therapy. Laboratory tests were performed at every administration. Adverse events (AEs) were assessed using NIC-CTC. Results: Twenty-one pts received BPs for more than 24 M. Median duration of administration of BPs was 48 M (24∼87 M), and 10 pts received BPs for more than 50 M. Eight pts were changed from PMT to INC. During treatment, there were no pathological fractures observed. No radiation or surgical treatment of bone was performed. Hypercalcemia was detected in 1 pt (4.8%). Lytic bone lesions changed to sclerotic lesions in 13 pts (61.9%). Improvement of PS was detected in 7 pts (33.3%). Hypocalcemia was seen in 13 pts (61.9%) but was not symptomatic. Leukopenia, thrombocytopenia and anemia were not observed. The baseline serum creatinine level was maintained and G1 serum creatinine elevation was seen in 4.8% of pts. G1 fatigue (19.0%), fever (13.3%), headache (4.8%) and diarrhea (4.8%) were detected. Major AEs were mild and transient. Conclusions: Severe AEs of long-term BP therapy were not seen. We conclude that long-term BP therapy was very effective and well-tolerated in BC pts with BM. AEs in this study were fewer than in previous reports. The optimal dose, duration and dosing interval for long-term BP therapy should be determined. No significant financial relationships to disclose.

Bisphosphonates in Metastatic Breast Cancer

Bone is the most common site of metastatic involvement in breast cancer. About 20–30% of patients with breast cancer have osseous metastases as the first site of metastatic disease and about 60–70% of patients will develop metastases to the bone during the course of their disease. Although bone metastases have usually only limited impact on overall survival, they cause significant morbidity due to pain, pathological fractures, hypercalcemic episodes or spinal cord compression. Bisphosphonates are a class of agents that can effectively reduce the number of serum calcium levels and activity of osteoclasts and therefore reduce bone complications in breast cancer. Bisphosphonates are the current standard of care in patients with tumour-induced hypercalcemia (TIH) since they achieve rapid normalisation in the majority of patients. Zoledronic acid, a third generation bisphosphonate, has recently been shown to be significantly more effective than the previous standard, pamidronate, in the treatment of TIH. In patients with bone metastases, large randomised clinical trials have shown the efficacy of bisphosphonates in addition to hormone therapy or chemotherapy in reducing and delaying skeletal complications and associated pain and in improving quality of life. A clear positive impact on overall survival, however, has not been observed. The optimal duration of treatment is currently unclear. Therefore, treatment with bisphosphonate should be continued until evidence of substantial decline in patient's general performance status. Until recently, best results were obtained with intermittent intravenous therapy with aminobisphosphonates resulting in a risk reduction of developing skeletal complications of at least 13%. There is evidence for a dose effect with pamidronate resulting in higher efficacy at doses of 90 mg compared to 45 or 60 mg. New data indicate a potential benefit of zoledronic acid over pamidronate in patients with osteolytic metastases. Oral bisphosphonates can also effectively reduce the risk of skeletal events. Treatment with oral aminobisphosphonate pamidronate was limited by gastrointestinal toxicity, however, oral ibandronate has recently been shown to be tolerable and highly effective. These data might increase the role of oral bisphosphonates in the treatment of metastatic breast cancer. In patients without evidence of bone involvement, three randomised trials have failed to show a clear benefit for bisphosphonates. Thus, bisphosphonate treatment cannot be recommended in this setting outside clinical trials. In conclusion bisphosphonates (intravenous or oral) are an effective treatment in patients with advanced breast cancer and clinically evidence bone metastases. They can reduce skeletal events and improve quality of life and are therefore recommended in all patients with bone metastases.

Napromienianie dwa razy dziennie podwyższoną dawką frakcyjną chorych z przerzutami nowotworów złośliwych do mózgu. Wyniki końcowe prospektywnego badania klinicznego w nierandomizowanej grupie chorych

Aim To evaluate the morbidity and effectivness of twice a day hypofractionation in patients with brain metastases. Material / methods Between 1992 and 2000, 116 patients with brain metastases have been treated with whole brain radiotherapy alone and only in 33 patients radiotherapy was applied as adjuvant treatment after surgery. Radiotherapy was given in two of 3 Gy fractions daily with minimum 6 hours intervals between fractions to total dose of 39 Gy. Mean age of treated patients was 55 years. All patients were in general performance status evaluated according to the Karnofsky Performance Scale of at least 50. Results Early tolerance of treatment was acceptable. Of 116 patients only 20 patients were treated with supportive treatment (anti-oedema drugs). Improvement of the neurological status was obtained in 26 patients (22%). The one-year overall survival was 21%. The one–year survival without clinical progression of disease was observed in 10% of all treated patients. Patients with solitary brain metastases treated with surgery and radiotherapy showed the best results. Conclusions Our results showed that twice a day hypo-fractionation radiotherapy for patients with brain metastases is well tolerated and may provides benefit.