Distribution Of Metastatic Sites Research Articles

Clinical outcomes of patients diagnosed with cancer of unknown primary or malignancy of undefined primary origin who were referred to a regional cancer center

BackgroundA regional cancer hospital has been identified to be crucial in the management of malignancies of undefined primary origin (MUO) and cancer of unknown primary (CUP). This hospital primarily consists of oncologists with expertise in CUP, pathologists, and interventional radiologists. Early consultation or referral of MUO and CUP to a cancer hospital is deemed important.MethodsThis study retrospectively collected and analyzed the clinical, pathological, and outcome data of all patients (n = 407) referred to the Aichi Cancer Center Hospital (ACCH) in Japan over an 8-year period.ResultsIn total, 30% of patients were referred for a second opinion. Among 285 patients, 13% had non-neoplastic disease or confirmed primary site and 76% had confirmed CUP (cCUP), with 29% of cCUP being identified as favorable risk. In 155 patients with unfavorable-risk CUP, 73% had primary sites predicted by immunohistochemistry (IHC) and distribution of metastatic sites, whereas 66% of them received site-specific therapies based on the predicted primary sites. The median overall survival (OS) was found to be poor in patients with MUO (1 month) and provisional CUP (6 months). In addition, the median OS of 206 patients with cCUP treated at the ACCH was 16 months (favorable risk, 27 months; unfavorable risk, 12 months). No significant difference was noted in OS between patients with non-predictable and predictable primary-sites (13 vs 12 months, p = 0.411).ConclusionThe outcome of patients with unfavorable-risk CUP remains to be poor. Site-specific therapy based on IHC is not recommended for all patients with unfavorable-risk CUP.

Abstract P4-07-07: Impact on overall survival according to sites of metastasis: Real-world data

Abstract Background Metastatic breast cancer, has a heterogeneous presentation and management, therefore its overall survival ranges from 2 to 3 years. Despite advances in breast cancer screening, diagnosis, and treatment, nearly 12-30% of early stage breast cancer patients eventually develop metastatic disease. In Ecuador, breast cancer is the most common malignancy among women, and the leading cause of newly diagnose cancer in the general population (Globocan 2020). This study aims to determine the frequency of metastatic sites and its impact in overall survival. Methods: An observational, retrospective, descriptive, single-center study was carried out. All patients with Metastatic breast cancer who had been treated at the National Oncology Institute SOLCA Guayaquil, in the period from 2016 to 2020 were included in the analysis. All statistical analyses were performed using SPSS for Windows (version 25.0;SPSS). The Kolmogorov-Smirnov test was used to test for the normality of distribution. Correlations were determined with Spearman correlation coefficients. The number of metastatic sites were recorded and their impact on overall survival was calculated by the Kaplan-Meier method and compared by the long-rank test, multivariable adjusted hazard ratios (HR) were estimated by Cox regression models. Results: A total of 1113 patients were included in the analysis, of which 84 patients (7.5%) were metastatic disease. The distribution of metastatic sites at diagnosis were: bone 64% (n=53), lung 51% (n=42), liver 30% (n=25), soft tissues 23% (n=19), and the least frequent were metastases to the central nervous system 17% (n=14), mediastinal lymph node 5% (n=4), peritoneal lymph node 1% (n=1). Regarding metastatic sites, 41% (N: 35) had only 1 metastatic site, 33,7% (N: 28) had 2 metastatic sites, and 25.3% (N:21) has 3 or more sites. A multivariable analysis was performed which takes into account all the metastases in the analysis. All have a higher risk of mortality vs not having any metastasis (all are greater than 1). But the only significant one is CNS with a RR 1,31 (1,08 - 1,61) P=0,005. Three or more sites of metastasis have RR 1,22 (0.95-1.57) p: 0.11. Relative Risk (RR) according to the different sites of metastasis are shown in the table#1. The association between 3 or more sites of metastasis showed a negative impact on overall survival (15 months +/-2.3 SD vs 36 months +/- 3.7 SD) compared to 1 site of metastasis. Conclusions: Approximately half of the women (N:49) with metastatic breast cancer in our population presented 2 or more sites of metastasis, which significantly decreases overall survival. The central nervous system is the site of metastasis with the highest relative risk of mortality, generating functional deterioration, adding morbidity, and only 64% (9 out of 14) of the patients access to radiotherapy as palliative treatment. Thus, better strategies for early diagnosis and adequate treatment of metastatic disease should be developed. Citation Format: Lissette Yagual Bohorquez, Evelyn Valencia-Espinoza, Emiliano Pulla-Cadmilema, Lissette P. Velez Avila, Maria del Mar Sanchez Salazar, Patricia Tamayo Aguilar, Jimmy Martin-Delgado, Glenda Ramos Martinez, Katherine Garcia Matamoros, Felipe Campoverde Merchan, Ruth Engracia Vivanco, Mayra Santacruz Maridueña, Roberto Escala Cornejo, Isabel Delgado Guerrero, Veronica Torres Floril, Diego Garcia Gamboa, Elina A. Rodriguez-Melendez. Impact on overall survival according to sites of metastasis: Real-world data [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-07.

Relationship Between Staging FDG PET/CT Findings and Distribution of Metastatic Sites in Metastatic Breast Cancer

Relationship Between Staging FDG PET/CT Findings and Distribution of Metastatic Sites in Metastatic Breast Cancer

Impact of the primary tumor location on secondary sites and overall mortality in patients with metastatic upper tract urothelial carcinoma.

To date it is unknown whether renal vs. ureteral urothelial carcinoma affects the type and the distribution of metastatic sites, and whether survival differs according to renal vs. ureteral location in metastatic patients. Two datasets were used, namely Surveillance, Epidemiology and End Results (SEER) and National Inpatients Sample (NIS). Multivariable logistic regression models tested whether renal pelvis vs. ureteral location predicts site-specific metastases. Kaplan-Meier plots and multivariable Cox regression models (CRMs) tested overall mortality (OM) according to renal pelvis vs. ureteral location. In SEER (2010-2016), 623 (71.1%) metastatic renal pelvis urothelial carcinoma (RPUC) vs. 253 (28.9%) ureteral urothelial carcinoma (UUC) patients were identified. Patients with RPUC more frequently harbored lung (46.1% vs. 35.2%, P < 0.01; Odds ratio [OR]: 1.57, P < 0.01), but less frequently liver metastases (27.9% vs. 36.4%, P = 0.02; OR:0.66, P = 0.01). In RPUC, lung, liver, bone, and brain metastases independently predicted higher OM. Only liver metastases independently predicted higher OM in UUC. In NIS (2005-2015), 818 (61.0%) RPUC vs. 522 (39.0%) UUC patients were identified. Patients with RPUC more frequently harbored lung (34.0% vs. 17.2%, P < 0.001; OR:2.36, P < 0.001), as well as brain (4.4% vs. 1.9%, P = 0.02; OR:2.00, P = 0.049) metastases, but less frequently harbored retroperitoneal and/or peritoneal (12.3% vs. 21.8%, P < 0.001; OR:0.51, P < 0.001), urinary tract (9.3% vs. 14.0%, P = 0.01; OR:0.65, P = 0.01) and multiple metastatic sites (62.6% vs. 70.7%, P < 0.01; OR:0.69, P < 0.01). In both databases lung metastases were more frequent in RPUC and abdominal metastases were more frequent in UUC. Moreover, liver metastases independently predicted worse survival, regardless of primary site.

Sex- and Age-Related Differences in the Distribution of Metastases in Patients With Upper Urinary Tract Urothelial Carcinoma.

The distribution of metastatic sites in upper tract urothelial carcinoma (UTUC) is not well-known. Consequently, the effects of sex and age on the location of metastases is also unknown. This study sought to investigate age- and sex-related differences in the distribution of metastases in patients with UTUC. Within the Nationwide Inpatient Sample database (2000-2015), we identified 1,340 patients with metastatic UTUC. Sites of metastasis were assessed according to age (≤63, 64-72, 73-79, and ≥80 years) and sex. Comparison was performed with trend and chi-square tests. Of 1,340 patients with metastatic UTUC, 790 (59.0%) were men (median age, 71 years) and 550 (41.0%) were women (median age, 74 years). The lung was the most common site of metastases in men and women (28.2% and 26.4%, respectively), followed by bone in men (22.3% vs 18.0% of women) and liver in women (24.4% vs 20.5% of men). Increasing age was associated with decreasing rates of brain metastasis in men (from 6.5% to 2.9%; P=.03) and women (from 5.9% to 0.7%; P=.01). Moreover, increasing age in women, but not in men, was associated with decreasing rates of lung (from 33.3% to 24.3%; P=.02), lymph node (from 28.9% to 15.8%; P=.01), and bone metastases (from 22.2% to 10.5%; P=.02). Finally, rates of metastases in multiple organs did not vary with age or sex (65.2% in men vs 66.5% in women). Lung, bone, and liver metastases are the most common metastatic sites in both sexes. However, the distribution of metastases varies according to sex and age. These observations apply to everyday clinical practice and may be used, for example, to advocate for universal bone imaging in patients with UTUC. Moreover, our findings may also be used for design considerations of randomized trials.

Abstract 4016: Personalizing the synergy of focal radiation and immunotherapy

Abstract Tumors grow within a host tissue that both facilitates progression by supplying nutrients and growth factors, and inhibits it through physical constraints and immune surveillance. Transformed cancer cells are confronted with this innate and adaptive immune surveillance, and tumors that develop to become clinically apparent have evolved to evade the immune system. This complex ecological system may be tipped back in favor of effective immune surveillance and tumor regression through novel immunotherapeutic strategies, particularly when used in concert with focal cytotoxic agents such as radiotherapy. We developed a multi-scale mathematical model framework to simulate local tumor-immune interactions as well as systemic distribution patterns of T cells activated locally in each metastatic site. We simulate focal radiotherapy-induced cytotoxicity and subsequent activation of an adaptive immune response, which may propagate systemically to cause regression of unirradiated metastases, known as the abscopal effect. We simulate concurrent anti-CTLA4 immunotherapy to investigate synergy. Model simulations suggest that systemic distribution of locally activated T cells is dependent on (i) the anatomical distribution of metastatic sites, (ii) the tumor volume of each metastasis, (iii) the site of focal therapy, (iv) the local therapy protocol of immune activation, and (v) the timing of concurrent immunotherapy. We find that irradiation of different metastatic sites has different likelihoods of inducing systemic tumor regressions. The developed framework can identify combination therapy protocols that optimally harness the synergy of focal therapy-induced immunity with immunotherapy, and identify optimum treatment targets on a per patient basis. Citation Format: Jan Poleszczuk, Kimberly Luddy, Shari Pilon-Thomas, Jonathan Schoenfeld, Heiko Enderling. Personalizing the synergy of focal radiation and immunotherapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4016.

Very late relapse metastatic renal cell carcinoma: Characteristics and outcomes of patients with a disease-free interval of greater than 10 years.

541 Background: Late relapse of renal cell carcinoma (RCC), or presentation with metastatic disease after a disease free interval of &gt;5 years, is a known behavior of RCC. Recent studies have concluded that late relapse RCC is associated with favorable patient and tumor characteristics as well as an improved response to targeted therapy (TT) when compared to early relapse patients. Less studied are patients who relapse very late, with a disease free interval &gt;10 years. We evaluated the clinical characteristics, response to TT and outcomes of this unique population. Methods: We collected data on consecutive patients with metastatic RCC who had disease recurrence &gt;10 years after nephrectomy. Outcomes were tabulated using basic statistical techniques; adverse events were graded using CTCAE v4.0 and treatment response graded using RECIST 1.1. Results: Among 720 RCC patients treated with nephrectomy, we identified 8 who developed recurrent metastatic disease after a &gt;10 year disease free interval (median: 16.7 years; range: 11.7-29.0). All patients presented with clear cell histology; 88% favorable IMDC and MSKCC risk subgroups. All patients presented with multiple metastases, with the most common sites being lung and bone, while unusual sites such as soft tissue, pancreas and adrenal were also detected. Median time on first-line TT was 20.1 months; 4, 3 and 1 patient received pazopanib (best response: PR), sunitinib (best response: SD) and cytokine (best response: PD) as first-line therapy, respectively. The median number of sequential TT received was 2 (range: 1-4). Four patients died, median OS was 46.6 months (range: 9.8-129), 3 year OS rate was 63%. Common adverse events to TT were fatigue (88%), anorexia (38%) and diarrhea (50%), 94% grade 1/2. Conclusions: Patients are at life-long risk of recurrence after resection of localized RCC as it is possible for metastases to present &gt;10 years after resection. Patients in our study had relatively large metastatic burden and a wide distribution of metastatic sites, insights that may be useful clinically during surveillance. Our cohort demonstrated favorable prognostic features and outcomes when compared to historical controls.

Beyond the Bone: Atypical Metastases in Prostate Cancer

The bone represents the most common site of metastases in patients with prostate cancer (PCa). However, the proportion of men experiencing atypical metastatic sites, defined as the metastases localizing to sites other than bones or lymph nodes outside the pelvis or abdomen, is significant. For example, 10.6%, 10.2% and 9.1% of patients with metastatic PCa experience distant lymph nodes, liver, and thorax involvement, respectively. The knowledge of the distribution of metastatic sites can help provide physicians with better staging strategies, as well as follow-up protocols aimed at a prompt diagnosis of tumor recurrence after primary treatment. The involvement of atypical sites of metastases might also have a prognostic value, where individuals with visceral metastases experience shorter survival compared to their counterparts with exclusive bone involvement. Consequently, this parameter should be taken in account during the decision-making process in the treatment of PCa patients.

233 Distribution of metastatic sites in bladder cancer: A population-based analysis

233 Distribution of metastatic sites in bladder cancer: A population-based analysis

Improved Survival of HER2-Positive Metastatic Breast Cancer in Routine Care

Purpose: Targeted therapy directed against HER2 has improved the outcome of patients with HER2-positive metastatic breast cancer in prospective clinical trials. No data are available how anti-HER2-therapy has influenced survival of unselected patients with HER2-positive metastatic breast cancer who receive treatment in routine care. Methods: Data of 118 subsequent patients with HER2-positive metastatic breast cancer who were treated in a community-based oncology group practice between 1995 and 2010 were analyzed retrospectively. Results: Median age at initial diagnosis of metastasis was 58 years (33-92). Twenty-two percent were metastasized at diagnosis of breast cancer, seventy-eight percent developed metastases in the course of the disease. Distribution of metastatic sites at initial diagnosis of metastasis was: 23% bone, 58% visceral, 5% CNS, 10% lymph nodes, 4% other. Hormone receptor was positive in 68% and negative in 31%. Palliative treatment consisted of antihormonal therapy in 56%, chemotherapy in 90% and radiotherapy in 50%. Seventy-five percent received anti-HER2-therapy consisting of trastuzumab in 80% and lapatinib in 1%, 19% received trastuzumab + lapatinib sequentially. Twenty-five percent received no anti-HER2-therapy. Median overall survival since initial diagnosis of metastasis was 34 months (0-277+). Conclusion: It could be shown that, compared to historical controls, targeted therapy against HER2 prolongs overall survival of patients with HER2-positive metastatic breast cancer who receive treatment in routine care.

Distribution of metastatic sites in renal cell carcinoma: a population-based analysis

We assessed the distribution of site-specific metastases in patients with renal cell carcinoma (RCC) according to age. Moreover, we evaluated recommendations proposed by guidelines and focused specifically on bone and brain metastases. Patients with metastatic RCC (mRCC) were abstracted from the Nationwide Inpatient Sample (1998-2007). Age was stratified into four groups: <55, 55-64, 65-74 and ≥ 75 years. Cochran-Armitage trend test and multivariable logistic regression analysis tested the relationship between age and the rate of multiple metastatic sites. Finally, we examined the rates of brain or bone metastases according to the presence of other metastatic sites. In 11,157 mRCC patients, the rate of multiple metastatic sites decreased with increasing age (P < 0.001). This phenomenon was confirmed in patients with lung, bone, liver and brain metastases (all P ≤ 0.01). The rate of bone metastases was 10% in patients with exclusive abdominal metastases and 49% in patients with abdominal, thoracic and brain metastases. The rate of brain metastases was 2% in patients with exclusive abdominal metastases and 16% in patients with thoracic and bone metastases. The proportion of patients with multiple metastatic sites is higher in young patients. The rates of bone (10%-49%) and brain (2%-16%) metastases are nonnegligible in mRCC patients.

P1-08-12: Hormonal Therapy Compliance and Mortality in Metastatic Breast Cancer.

Abstract Methods: A retrospective analysis was conducted using linked pharmacy claims and cancer registry data from the population-based National Cancer Registry Ireland (NCRI). Women with stage IV breast cancer at initial diagnosis (2004-2006), who received HTx as 1st line treatment for ≥90 days were identified (tamoxifen, toremifene, fulvestrant, anastrozole, letrozole, exemestane). Compliance was calculated over the time that patients remained on HTx i.e. from the date of treatment initiation to the earliest of either HTx discontinuation or end of follow up (31/12/07, 3 years or death). Patients discontinuing HTx were assigned their compliance rate at this time for the remainder of follow-up. In the primary analysis Cox proportional hazard models with late entry at 90 days post HTx initiation and time varying compliance (defined dichotomously as: low &amp;lt; 80%, high ≥ 80%), were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for all-cause and breast cancer specific mortality. Secondary analyses of (a) time to treatment discontinuation and (b) compliance in the first 90 days of treatment were conducted. All models were adjusted for age, tumor grade, number/site of metastases, estrogen, progesterone and human epidermal growth factor 2 receptor status. Results: 359 women with stage IV breast cancer at diagnosis were identified. Of these, 151 received HTx as 1st line treatment. Median HTx compliance was 84.8%, (range 19.4%-100%; interquartile range 75.5%-100%). Demographic, tumor and treatment characteristics were similar between low (n=51) and high (n=100) compliance groups. The number and distribution of metastatic sites at diagnosis was also similar (low/high compliance: bone only 70.6%/70.0%, lung only 17.6%/18.0%, liver only 11.8%/14.0%, brain only 0.0%/0.0%, other 13.7%/17.0%, multiple sites 15.7%/18.0%). Compliance rates for both compliance groups increased marginally over time. Unadjusted all-cause mortality rates were 143 and 359 deaths/1000 woman years for low and high compliance respectively. Low compliance was associated with a 90% increased risk of all-cause (HR 1.90; 95%CI 1.06, 3.41) and breast cancer specific (HR 1.91; 95%CI 1.03, 3.55) mortality. In the secondary analyses low compliance was associated with a shorter time to HTx discontinuation (HR 1.97; 95%CI 1.01, 3.84). Low compliance within the first 90 days of treatment was associated with non-significantly increased mortality (all-cause HR 1.57; 95%CI 0.88, 2.80; breast cancer specific HR 1.58; 95%CI 0.85, 2.93). Discussion: This study demonstrates, for the first time to our knowledge, a significant association between low HTx compliance and increased mortality in patients with MBC. In addition, the observed association between compliance and treatment duration is consistent with a reduced time to disease progression in low compliance patients. The findings do not appear to be related to either the burden of metastatic disease at diagnosis or to increasing disease severity causing lower compliance over time. These results suggest that the development and evaluation of effective interventions to support HTx compliance in patients with MBC is warranted. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-08-12.

Metastatic patterns at autopsy in patients with ovarian carcinoma

Previously published studies concerning autopsy findings in ovarian cancer failed to consider the broad differences in factors that influence the course of disease. Furthermore, those studies were conducted when the currently accepted standards in diagnostics and therapy had not been fully established. The objective of the current study was to determine the frequency and sites of metastases in patients with ovarian cancer with particular attention to the clinical course and therapy. Autopsy reports, histologic slides, and clinical files from 197 patients who died of ovarian carcinoma between 1975 and 2005 were studied. The distribution of metastatic sites (19 different organ sites) and metastatic patterns, with particular attention to clinical course (age, length of survival) and therapy (surgical treatment with curative intention, different chemotherapy regimens), were analyzed. Overall, 66.3% of patients had metastases to sites outside the abdominopelvic cavity. Patients who were aged >70 years, who had a disease duration <or=6 months, or who had received either no treatment or treatment without curative intention more often had metastases limited to the abdominopelvic cavity. This pattern of spread was observed most frequently in patients who had received current chemotherapy regimens (odds ratio, 3.5; P = .002). Compared with patients who had received chemotherapy according to previous standards, these patients showed a significantly increased incidence of liver metastases (P < .001). Autopsy data may yield important information concerning the metastatic potential of a malignancy and may assist physicians in making clinical management decisions. The results from the current indicated that declining autopsy rates during the last decades have limited the ability of physicians to evaluate the impact of new therapy regimens on the frequency and distribution of metastases through postmortem examination.

A Retrospective Study of First Indicators of Breast Cancer Recurrence

This study was performed to evaluate the first indicators of breast cancer recurrence in 1,145 patients treated at the University of Texas MD Anderson Cancer Center, between July 1973 and December 1980. Twenty patients were excluded due to incomplete data, resulting in a total number of 1,125 evaluable patients. Data collection included the first metastatic site and its means of detection (symptoms, self-examination, physical examination performed by a physician, and the results of blood and radiological tests). Whether recurrence was found at the scheduled follow-up visits or between the scheduled visits was also analyzed. Symptoms were the primary indicator of relapse for 648 cases (57.6% of the study population). An additional 361 cases (32.1% of the total group) were detected by self-examination or by physician-performed physical examination. Other investigations, e.g. bone scans, liver scans, chest X-rays, and blood tests, revealed recurrent disease in only 116 patients (10.3% of the population). Among the 1,125 patients, 254 recurrences (22.6% of the study population) were detected at the scheduled follow-up surveillance and, among these, 64.6% were found by history or physical examination. The distribution of metastatic sites and first indicators of metastases remained constant over time. The scheduled follow-up visits detected a mean of 25.9% of relapses during the first 36 months, while after 36 months only 16.3% of relapses were detected by systematic monitoring. There were no statistically significant differences in disease-free overall survival rates between symptomatic and asymptomatic patients at the time the first recurrence was detected. Moreover, the disease-free and overall survival rates appeared to be the same in symptomatic and asymptomatic patients, whether or not the recurrence was detected by a scheduled follow-up examination. Two conclusions emerged from the present study. Extensive, routine laboratory investigations are not justifiable following curative treatment of primary breast cancer, and it seems reasonable and cost-effective to reduce follow-up surveillance to careful history and physical examination only. The actual method of surveillance does not significantly affect the time interval to metastasis detection and seems inefficient. Clearly, more sensitive methods are needed for earlier detection of recurrent metastatic breast cancer. In addition, early detection of metastases would be even more valuable if more effective treatment modalities of recurrent or metastatic breast cancer were available.

Prospective randomized comparison of fluorouracil versus fluorouracil and high-dose continuous infusion leucovorin calcium for the treatment of advanced measurable colorectal cancer in patients previously unexposed to chemotherapy.

Seventy-nine patients with advanced, measurable, metastatic colorectal cancer previously unexposed to chemotherapy were randomly assigned to treatment with either fluorouracil (FUra) administered intravenously at a dose of 370 mg/m2/d for 5 days or the combination of FUra in the same dose and schedule with high-dose continuous infusion leucovorin calcium (500 mg/m2/d) beginning 24 hours before the first dose of FUra and continuing for 12 hours after the completion of FUra therapy. Patients whose disease progressed on treatment with FUra alone were, if eligible, crossed over to receive leucovorin and FUra. Three patients on the FUra plus leucovorin arm of the study were excluded from the analysis because they did not meet eligibility requirements. The treatment arms were well balanced for prognostic criteria including performance status, age, prior radiotherapy, distribution of metastatic sites, and on-study carcinoembryonic antigen (CEA), lactic dehydrogenase, and serum albumin. FUra plus leucovorin was superior to FUra alone for response (P = .0019) and for time to progression or death (log-rank, P = .045). Response rates were 16 of 36 (44%) versus five of 40 (13%), and median time to progression or death was 164 versus 120 days in the two arms of the trial, respectively. Overall survival, however, while longer in the FUra and leucovorin arm was not significantly so. An analysis of the toxicities experienced by the patients in the two treatment groups showed that, except for significantly more stomatitis in the leucovorin arm of the study, the side effects experienced by patients treated with either regimen were comparable. These results suggest that the efficacy of FUra in patients with advanced, measurable, metastatic colorectal cancer can be enhanced significantly by administration of a continuous high-dose infusion of leucovorin calcium.

The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in small-cell lung cancer.

Review of clinical data from 350 patients with small-cell lung cancer (SCLC) revealed hyponatremia (sodium less than 130 mEq/L) attributable to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in 40 patients (11%). Although hyponatremia was severe in most instances (median, sodium 117 mEq/L), symptoms attributable to water intoxication were identified in only 27% of hyponatremic episodes. Development of SIADH showed no correlation with clinical stage, distribution of metastatic sites, sex, or histologic subtype of small-cell carcinoma. SIADH occurred most often with initial presentation (33 of 40), and resolved promptly (less than 3 weeks) with initiation of combination chemotherapy in 80% of evaluable patients. The presence of SIADH did not influence response to chemotherapy or overall survival as an independent variable. However, in five patients profound hyponatremia developed immediately following primary cytotoxic therapy (range, one to five days). Despite initial control of SIADH, dilutional hyponatremia recurred in 70% of patients with tumor progression. Our findings suggest that development of clinically demonstrable SIADH in patients with SCLC is dependent on functional properties of the neoplastic cells, rather than tumor burden or metastatic site. The potential for development of clinically significant hyponatremia early in the course of cytotoxic therapy emphasizes the need to closely monitor patients, particularly those receiving chemotherapy regimens requiring substantial intravenous hydration.