Cancer

Doxorubicin is a highly effective and widely used cytotoxic agent with application that is limited by cardiotoxicity related to the cumulative dose of the drug. A large‐scale study that retrospectively evaluated the cardiotoxicity of doxorubicin reported that an estimated 7% of patients developed doxorubicin‐related congestive heart failure (CHF) after a cumulative dose of 550 mg/m². To assess whether this estimate is reflective of the incidence in the broader clinical oncology setting, the authors evaluated data from three prospective studies to determine both the incidence of doxorubicin‐related CHF and the accumulated dose of doxorubicin at which CHF occurs.

A group of 630 patients who were randomized to a doxorubicin‐plus‐placebo arm of three Phase III studies, two studies in patients with breast carcinoma and one study in patients with small cell lung carcinoma, were included in the analysis.

Thirty‐two of 630 patients had a diagnosis of CHF. Analysis indicated that an estimated cumulative 26% of patients would experience doxorubicin‐related CHF at a cumulative dose of 550 mg/m². Age appeared to be an important risk factor for doxorubicin‐related CHF after a cumulative dose of 400 mg/m², with older patients (age > 65 years) showing a greater incidence of CHF compared with younger patients (age ≤ 65 years). In addition, > 50% of the patients who experienced doxorubicin‐related CHF had a reduction < 30% in left ventricular ejection fraction (LVEF) while they were on study.

Doxorubicin‐related CHF occurs with greater frequency and at a lower cumulative dose than previously reported. These findings further indicate that LVEF is not an accurate predictor of CHF in patients who receive doxorubicin. Cancer 2003;97:2869–79. © 2003 American Cancer Society.

DOI 10.1002/cncr.11407

Osteosarcoma, which is the most common primary bone tumor, occurs most frequently in adolescents, but there is a second incidence peak among individuals aged >60 years. Most osteosarcoma epidemiology studies have been embedded in large analyses of all bone tumors or focused on cases occurring in adolescence. Detailed descriptions of osteosarcoma incidence and survival with direct comparisons among patients of all ages and ethnicities are not available.

Frequency, incidence, and survival rates for 3482 patients with osteosarcoma from the National Cancer Institute's population‐based Surveillance, Epidemiology, and End Results (SEER) Program between 1973 and 2004 were investigated by age (ages 0‐24 years, 25‐59 years, and 60 to ≥85 years), race, sex, pathology subtype, stage, and anatomic site.

There were large differences in incidence and survival rates by age. There was a high percentage of osteosarcoma with Paget disease and osteosarcoma as a second or later cancer among the elderly. There was a high percentage of osteosarcoma among patients with Paget disease and osteosarcoma as a second or later cancer among the elderly. Tumor site differences among age groups were noted. Survival rates varied by anatomic site and disease stage and did not improve significantly from 1984 to 2004.

This comprehensive, population‐based description of osteosarcoma, identified important differences in incidence, survival, pathologic subtype, and anatomic site among age groups, and quantified the impact of osteosarcoma in patients with Paget disease or as a second cancer on incidence and mortality rates. These findings may have implications in understanding osteosarcoma biology and epidemiology. Cancer 2009. © 2009 American Cancer Society.

Recent breakthroughs regarding gastrointestinal stromal tumors (GIST) and their pathogenesis have redefined diagnostic criteria and have led to the development of molecularly targeted drug therapy. New treatment options mandate more accurate information regarding the incidence, prevalence, clinical behavior, and prognostic factors of GIST.

All patients (n = 1460) who potentially had GIST diagnosed from 1983 to 2000 in western Sweden (population, 1.3–1.6 million) were reviewed, and 288 patients with primary GIST were identified. The incidence and prevalence of GIST were determined, and predictive prognostic factors, including current risk‐group stratifications, were analyzed statistically.

Ninety percent of GISTs were detected clinically due to symptoms (69%) or were incidental findings at surgery (21%); the remaining 10% of GISTs were found at autopsy. Forty‐four percent of symptomatic, clinically detected GISTs were categorized as high risk (29%) or overtly malignant (15%), with tumor‐related deaths occurring in 63% of patients and 83% of patients, respectively (estimated median survival, of 40 months and 16 months, respectively). Tumor‐related deaths occurred in only 2 of 170 of patients (1.2%) with very‐low‐risk, low‐risk, or intermediate‐risk tumors. The annual incidence of GIST was 14.5 per million. The prevalence of all GIST risk groups was 129 per million (31 per million for the high‐risk group and the overtly malignant group).

GIST has been under recognized: Its incidence, prevalence, and clinical aggressiveness also have been underestimated. Currently existing risk‐group stratification systems based on tumor size and mitotic rate delineate GIST patients who have a poor prognosis. Prognostication in patients with GIST can be refined using a proposed risk score based solely on tumor size and proliferative index. Cancer 2005. © 2005 American Cancer Society.

Women with HER‐2 overexpressing metastatic breast carcinoma benefit from trastuzumab‐based therapy, but trastuzumab does not cross the blood‐brain barrier. The authors characterized central nervous system (CNS) disease in these women.

Using pharmacy records, the authors retrospectively identified 153 women treated with trastuzumab alone or with chemotherapy for HER‐2–positive metastatic breast carcinoma at Dana‐Farber Partners Cancer Care from June 1998 to December 2000. A study cohort of 122 patients was identified after excluding patients without adequate clinical follow‐up or who had CNS disease before trastuzumab treatment. Central nervous system disease was defined as one or more brain metastases or as leptomeningeal carcinomatosis. The median follow‐up of this cohort was 23 months.

Central nervous system metastases were identified in 34% of patients (95% confidence interval, 26–44%) at a median of 16 months after diagnosis of metastatic breast carcinoma and 6 months from the beginning of trastuzumab therapy. Ninety‐three percent of patients with CNS disease presented with clinical symptoms. Five percent of patients with CNS disease had leptomeningeal involvement alone, although 14% had leptomeningeal involvement and parenchymal brain metastases. Fifty percent of patients were responding or had stable disease while receiving trastuzumab at other disease sites at the time of diagnosis of CNS metastasis. The median survival period after CNS metastases was 13 months. Fifty percent of patients died of progressive CNS disease. Patients receiving trastuzumab as first‐line therapy for metastatic disease frequently developed brain metastases while responding to or stable on trastuzumab at other disease sites.

Metastatic breast carcinoma to the CNS is common among patients receiving trastuzumab‐based therapy, including patients responding to therapy outside the CNS. This may be due either to predilection for the CNS by HER‐2–positive tumor cells and/or poor penetration of the CNS by trastuzumab or to improved visceral disease control leading to a longer life and onset of late tumor spread to the CNS. Efforts to characterize other risk factors for development of CNS disease, optimal screening algorithms, and new treatment strategies may be warranted. Cancer 2003;97:2972–7. © 2003 American Cancer Society.

DOI 10.1002/cncr.11436

The American Cancer Society (ACS), the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR) collaborate annually to provide updates on cancer incidence and death rates and trends in these outcomes for the United States. This year's report includes the prevalence of comorbidity at the time of first cancer diagnosis among patients with lung, colorectal, breast, or prostate cancer and survival among cancer patients based on comorbidity level.

Data on cancer incidence were obtained from the NCI, the CDC, and the NAACCR; and data on mortality were obtained from the CDC. Long‐term (1975/1992‐2010) and short‐term (2001‐2010) trends in age‐adjusted incidence and death rates for all cancers combined and for the leading cancers among men and women were examined by joinpoint analysis. Through linkage with Medicare claims, the prevalence of comorbidity among cancer patients who were diagnosed between 1992 through 2005 residing in 11 Surveillance, Epidemiology, and End Results (SEER) areas were estimated and compared with the prevalence in a 5% random sample of cancer‐free Medicare beneficiaries. Among cancer patients, survival and the probabilities of dying of their cancer and of other causes by comorbidity level, age, and stage were calculated.

Death rates continued to decline for all cancers combined for men and women of all major racial and ethnic groups and for most major cancer sites; rates for both sexes combined decreased by 1.5% per year from 2001 through 2010. Overall incidence rates decreased in men and stabilized in women. The prevalence of comorbidity was similar among cancer‐free Medicare beneficiaries (31.8%), breast cancer patients (32.2%), and prostate cancer patients (30.5%); highest among lung cancer patients (52.9%); and intermediate among colorectal cancer patients (40.7%). Among all cancer patients and especially for patients diagnosed with local and regional disease, age and comorbidity level were important influences on the probability of dying of other causes and, consequently, on overall survival. For patients diagnosed with distant disease, the probability of dying of cancer was much higher than the probability of dying of other causes, and age and comorbidity had a smaller effect on overall survival.

Cancer death rates in the United States continue to decline. Estimates of survival that include the probability of dying of cancer and other causes stratified by comorbidity level, age, and stage can provide important information to facilitate treatment decisions. Cancer 2014;120:1290–1314. © 2013 American Cancer Society.

The literature on upper tract urothelial carcinoma (UTUC) has been limited to small, single center studies. A large series of patients treated with radical nephroureterectomy for UTUC were studied, and variables associated with poor prognosis were identified.

Data on 1363 patients treated with radical nephroureterectomy at 12 academic centers were collected. All pathologic slides were re‐reviewed by genitourinary pathologists according to strict criteria.

Pathologic review revealed renal pelvis location (64%), necrosis (21.6%), lymphovascular invasion (LVI) (24.8%), concomitant carcinoma in situ (28.7%), and high‐grade disease (63.7%). A total of 590 patients (43.3%) underwent concurrent, lymphadenectomy and 135 (9.9%) were lymph node (LN) ‐positive. Over a mean follow‐up of 51 months, 379 (28%) patients experienced disease recurrence outside of the bladder and 313 (23%) died of UTUC. The 5‐year recurrence‐free and cancer‐specific survival probabilities (±SD) were 69% ± 1% and 73% ± 1%, respectively. On multivariate analysis, high tumor grade (hazards ratio [HR]: 2.0, P < .001), advancing pathologic T stage (P‐for‐trend <.001), LN metastases (HR: 1.8, P < .001), infiltrative growth pattern (HR: 1.5, P < .001), and LVI (HR: 1.2, P = .041) were associated with disease recurrence. Similarly, patient age (HR: 1.1, P = .001), high tumor grade (HR: 1.7, P = .001), increasing pathologic T stage (P‐for‐trend <.001), LN metastases (HR: 1.7, P < .001), sessile architecture (HR: 1.5, P = .002), and LVI (HR: 1.4, P = .02) were independently associated with cancer‐specific survival.

Radical nephroureterectomy provided durable local control and cancer‐specific survival in patients with localized UTUC. Pathologic tumor grade, T stage, LN status, tumor architecture, and LVI were important prognostic variables associated with oncologic outcomes, which could potentially be used to select patients for adjuvant systemic therapy. Cancer 2009. © 2009 American Cancer Society.