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BACKGROUND The objective of this study was to describe bladder cancer outcomes as a function of race among patients with high-risk non-muscle-invasive bladder cancer (NMIBC) in an equal-access setting. METHODS A total of 412 patients with high-risk NMIBC who received bacille Calmette-Guerin (BCG) from January 1, 2010, to December 31, 2015, were assessed. The authors used the Kaplan-Meier method to estimate event-free survival and Cox regression to determine the association between race and recurrence, progression, disease-specific, and overall survival outcomes. RESULTS A total of 372 patients who had complete data were included in the analysis; 48 (13%) and 324 (87%) were Black and White, respectively. There was no difference in age, sex, smoking status, or Charlson Comorbidity Index by race. White patients had a higher socioeconomic status with a greater percentage of patients living above the poverty level in comparison with Black patients (median, 85% vs 77%; P < .001). A total of 360 patients (97%) received adequate induction BCG, and 145 patients (39%) received adequate maintenance BCG therapy. There was no significant difference in rates of adequate induction or maintenance BCG therapy according to race. There was no significant difference in recurrence (hazard ratio [HR], 1.53; 95% confidence interval [CI], 0.64-3.63), progression (HR, 0.77; 95% CI, 0.33-1.82), bladder cancer-specific survival (HR, 1.01; 95% CI, 0.30-3.46), or overall survival (HR, 0.97; 95% CI, 0.56-1.66) according to Black race versus White race. CONCLUSIONS In this small study from an equal-access setting, there was no difference in the receipt of BCG or any differences in bladder cancer outcomes according to race.

BACKGROUND: Disparity in mental health care among cancer patients remains understudied. METHODS: We conducted a large, retrospective, single tertiary-care institution cohort study based on de-identified electronic health record data of 54,852 adult cancer patients without prior mental health diagnosis (MHD) diagnosed at the University of California, San Francisco between 1/2012 and 9/2019. The exposure of interest was early onset MHD with or without psychotropic medication (PM) within 12 months of cancer diagnosis and primary outcome was all-cause mortality. RESULTS: 8.2% of patients received a new MHD at a median of 197 days (interquartile-range [IQR] 61-553) after incident cancer diagnosis, 31.0% received a PM prescription, and 3.7% a MHRV. 62.6% of patients were non-Hispanic white (NHW), 10.8% Asian, 9.8% Hispanic, and 3.8% Black. Compared to NHWs, minority cancer patients had reduced adjusted odds of MHDs, PM prescriptions, and MHRVs, particularly for generalized anxiety (Asian: odds ratio [OR] 0.66, 95% confidence interval 0.55-0.78; Black: OR 0.60, 0.45-0.79; Hispanic: OR 0.72, 0.61-0.85) and selective-serotonin-reuptake-inhibitors (SSRI; Asian: OR 0.43, 0.37-0.50; Black: OR 0.51, 0.40-0.61; Hispanic: OR 0.79, 0.70-0.89). New early MHD with PM was associated with elevated all-cause mortality (12-24 months: hazard ratio [HR] 1.43, 1.25-1.64) that waned by 24-36 months (HR 1.18, 0.95-1.45). CONCLUSIONS AND RELEVANCE: New mental health diagnosis with psychotropic medication was a marker of early mortality among cancer patients. Minority cancer patients were less likely to receive documentation of mental health diagnoses or treatment, which may represent missed opportunities to identify and treat cancer related mental health conditions.

BACKGROUND Although skeletal-related events (SREs) are linked with a reduced quality of life and worse outcomes, to the authors' knowledge the factors that predict SREs are minimally understood. The objective of the current study was to identify predictors of SREs and all-cause mortality among men with metastatic castration-resistant prostate cancer (mCRPC). METHODS Data were collected on 837 men with bone mCRPC at 8 Veterans Affairs medical centers within the Shared Equal Access Regional Cancer Hospital (SEARCH) database from 2000 through 2017. Patients were followed to assess development of SREs (pathological fracture, radiotherapy to bone, spinal cord compression, or surgery to bone). Cox proportional hazards models were used to evaluate predictors of SREs and mortality. RESULTS Of the 837 men with bone mCRPC, 287 developed a SRE and 740 men died (median follow-up, 26 months). Bone pain was found to be the strongest predictor of SREs (hazard ratio [HR], 2.96; 95% CI, 2.25-3.89). A shorter time from CRPC to the development of metastasis (HR, 0.92; 95% CI, 0.85-0.99), shorter progression to CRPC (HR, 0.94; 95% CI, 0.91-0.98), and visceral metastasis at the time of diagnosis of bone metastasis (HR, 1.91; 95% CI, 1.18-3.09) were associated with an increased risk of SREs. Ten or more bone metastases (HR, 2.17; 95% CI, 1.72-2.74), undergoing radical prostatectomy (HR, 0.73; 95% CI, 0.61-0.89), shorter progression to CRPC (HR, 0.97; 95% CI, 0.94-0.99), older age (HR, 1.03; 95% CI, 1.02-1.04), higher prostate-specific antigen level at the time of diagnosis of metastasis (HR, 1.21; 95% CI, 1.14-1.28), bone pain (HR, 1.44; 95% CI, 1.23-1.70), and visceral metastasis (HR, 1.72; 95% CI, 1.23-2.39) were associated with an increased mortality risk. CONCLUSIONS Among men with bone mCRPC, bone pain was found to be the strongest predictor of SREs and the number of bone metastases was a strong predictor of mortality. If validated, these factors potentially may be used for risk stratification and for SRE prevention strategies.

Background This study was designed to adapt the Elixhauser comorbidity index for 4 cancer-specific populations (breast, prostate, lung, and colorectal) and compare 3 versions of the Elixhauser comorbidity score (individual comorbidities, summary comorbidity score, and cancer-specific summary comorbidity score) with 3 versions of the Charlson comorbidity score for predicting 2-year survival with 4 types of cancer. Methods This cohort study used Texas Cancer Registry-linked Medicare data from 2005 to 2011 for older patients diagnosed with breast (n = 19,082), prostate (n = 23,044), lung (n = 26,047), or colorectal cancer (n = 16,693). For each cancer cohort, the data were split into training and validation cohorts. In the training cohort, competing risk regression was used to model the association of Elixhauser comorbidities with 2-year noncancer mortality, and cancer-specific weights were derived for each comorbidity. In the validation cohort, competing risk regression was used to compare 3 versions of the Elixhauser comorbidity score with 3 versions of the Charlson comorbidity score. Model performance was evaluated with c statistics. Results The 2-year noncancer mortality rates were 14.5% (lung cancer), 11.5% (colorectal cancer), 5.7% (breast cancer), and 4.1% (prostate cancer). Cancer-specific Elixhauser comorbidity scores (c = 0.773 for breast cancer, c = 0.772 for prostate cancer, c = 0.579 for lung cancer, and c = 0.680 for colorectal cancer) performed slightly better than cancer-specific Charlson comorbidity scores (ie, the National Cancer Institute combined index; c = 0.762 for breast cancer, c = 0.767 for prostate cancer, c = 0.578 for lung cancer, and c = 0.674 for colorectal cancer). Individual Elixhauser comorbidities performed best (c = 0.779 for breast cancer, c = 0.783 for prostate cancer, c = 0.587 for lung cancer, and c = 0.687 for colorectal cancer). Conclusions The cancer-specific Elixhauser comorbidity score performed as well as or slightly better than the cancer-specific Charlson comorbidity score in predicting 2-year survival. If the sample size permits, using individual Elixhauser comorbidities may be the best way to control for confounding in cancer outcomes research. Cancer 2018;124:2018-25. © 2018 American Cancer Society.

BACKGROUND The objective of this study was to compare the overall survival of patients who undergo radical prostatectomy or radiotherapy versus noncancer controls to discern whether there is a survival advantage according to prostate cancer treatment and the impact of selection bias on these results. METHODS A matched cohort study was performed using the Surveillance, Epidemiology, and End Results (SEER)-Medicare–linked database. In total, 34,473 patients ages 66 to 75 years were identified who were without significant comorbidity, were diagnosed with localized prostate cancer, and received treatment treated with surgery or radiotherapy between 2004 and 2011. These patients were matched to a noncancer control cohort. The rates of all-cause mortality that occurred within the study period were compared. Cox proportional hazards regression analysis was used to identify determinants associated with overall survival. RESULTS Of 34,473 patients who were included in the analysis, 21,740 (63%) received radiation therapy, and 12,733 (37%) underwent surgery. There was improved survival in patients who underwent surgery (hazard ratio, 0.35; 95% confidence interval, 0.32-0.38) and in those who received radiotherapy (hazard ratio, 0.72; 95% confidence interval, 0.68-0.75) compared with noncancer controls. Overall survival improved significantly in both treatment groups, with the greatest benefit observed among patients who underwent surgery (log rank P

Background Previous studies have demonstrated an association between a diagnosis of cancer and the risk of suicide; however, they failed to account for psychiatric care before a cancer diagnosis, which may confound this relationship. The objective of this study was to assess the effect of a cancer diagnosis on the risk of suicide, accounting for prediagnosis psychiatric care utilization. Methods All adult residents of Ontario, Canada who were diagnosed with cancer (1 of prostate, breast, colorectal, melanoma, lung, bladder, endometrial, thyroid, kidney, or oral cancer) between 1997 and 2014 were identified. Noncancer controls were matched 4:1 based on sociodemographics, including a psychiatric utilization gradient (PUG) score (with 0 indicating none; 1, outpatient; 2, emergency department; and 3, hospital admission). A marginal, cause-specific hazard model was used to assess the effect of cancer on the risk of suicidal death. Results Among 676,470 patients with cancer and 2,152,682 matched noncancer controls, there were 8.2 and 11.4 suicides per 1000 person-years of follow-up, respectively. Patients with cancer had an overall higher risk of suicidal death compared with matched patients without cancer (hazard ratio, 1.34; 95% CI, 1.22-1.48). This effect was pronounced in the first 50 months after cancer diagnosis (hazard ratio, 1.60; 95% CI, 1.42-1.81); patients with cancer did not demonstrate an increased risk thereafter. Among individuals with a PUG score 0 or 1, those with cancer were significantly more likely to die of suicide compared with controls. There was no difference in suicide risk between patients with cancer and controls for those who had a PUG score of 2 or 3. Conclusions A cancer diagnosis is associated with increased risk of death from suicide compared with the general population even after accounting for precancer diagnosis psychiatric care utilization. The specific factors underlying the observed associations remain to be elucidated.

BACKGROUND Despite recent interest in the overdiagnosis and overtreatment of prostate cancer, the acceptance of expectant management for patients with indolent prostate cancer has remained slow. Moreover, the intensity of surveillance strategies remains to be elucidated. The objective of this study was to determine the population-based intensity of surveillance strategy among patients diagnosed with localized prostate cancer who undergo watchful waiting/active surveillance and those who receive active treatment. METHODS Linked Surveillance, Epidemiology, and End Results (SEER)-Medicare data were used to identify men diagnosed with prostate cancer from 2004 to 2007 who were followed until December 31, 2009. Bivariate and multivariate regression analyses were used to quantify the use of prostate-specific antigen tests, office visits, and second prostate biopsies within 2 years of diagnosis. RESULTS Compared with patients who were receiving active treatment, those who were undergoing watchful waiting/active surveillance were less likely to receive prostate-specific antigen testing and to attend office visits within the 2 years after diagnosis (P

BACKGROUND Treatments for muscle-invasive bladder cancer are multimodal, complex, and often carry significant risks of physical and psychological morbidity. The objectives of this study were to define the incidence and types of psychiatric illnesses diagnosed after treatment and to determine their impact on survival outcomes. METHODS In total, 3709 patients who were diagnosed with clinical stage T2 through T4a bladder cancer from January 1, 2002, to December 31, 2011, from the Surveillance, Epidemiology, and End Results-Medicare were analyzed. Multivariable analysis and Cox proportional-hazards models were used to determine the predictors associated with psychiatric diagnosis and impact on survival outcomes. RESULTS Of 3709 patients, 1870 (50.4%) were diagnosed with posttreatment psychiatric disorders. Patients who underwent radical cystectomy were identified as being at significantly greater risk of having a posttreatment psychiatric illness compared with those who received radiotherapy and/or chemotherapy (hazard ratio [HR], 1.19; 95% confidence interval [CI], 1.07-1.31; P = .001). In adjusted analyses, diagnosis of a psychiatric disorder resulted in significantly worse overall survival (HR, 2.80; 95% CI, 2.47-3.17; P

Limited survival benefit and excess treatment because of prostate-specific antigen (PSA) screening in randomized trials suggests a need for more restricted selection of prostate biopsy candidates by discerning risk of histologically aggressive versus indolent cancer before biopsy.Subjects undergoing first prostate biopsy enrolled in a multicenter, prospective cohort of the National Cancer Institute Early Detection Research Network (N = 635) were analyzed to develop a model for predicting histologically aggressive prostate cancers. The control arm of the Prostate Cancer Prevention Trial (N = 3833) was used to validate the generalization of the predictive model.The Early Detection Research Network cohort was comprised of men among whom 57% had no cancer, 14% had indolent cancer, and 29% had aggressive cancer. Age, body mass index, family history of prostate cancer, abnormal digital rectal examination (DRE), and PSA density (PSAD) were associated with aggressive cancer (all P.001). The Early Detection Research Network model outperformed PSA alone in predicting aggressive cancer (area under the curve [AUC] = 0.81 vs 0.71, P.01). Model validation in the Prostate Cancer Prevention Trial cohort accurately identified men at low (10%) risk of aggressive cancer for whom biopsy could be averted (AUC = 0.78; 95% confidence interval, 0.75-0.80). Under criteria from the Early Detection Research Network model, prostate biopsy can be restricted to men with PSAD0.1 ng/mL/cc or abnormal DRE. When PSAD is0.1 ng/mL/cc, family history or obesity can identify biopsy candidates.A predictive model incorporating age, family history, obesity, PSAD, and DRE elucidates criteria whereby ¼ of prostate biopsies can be averted while retaining high sensitivity in detecting aggressive prostate cancer.

BACKGROUND: We sought to identify the costs of adjuvant therapies following radical prostatectomy (RP) and factors associated with their receipt. METHODS: We used SEER-Medicare data from 2004-2006 to identify 4247 men who underwent RP, of whom 600 subsequently received adjuvant therapies. We used Cox regression to identify factors associated with receipt of adjuvant therapies. Health care expenditures within 12 months of diagnosis were compared for RP alone versus RP with adjuvant therapies. RESULTS: Biopsy Gleason score, prostate-specific antigen, risk group, and SEER region were significantly associated with receipt of adjuvant treatments (all P

Despite recent interest in the overdiagnosis and overtreatment of prostate cancer, the acceptance of expectant management for patients with indolent prostate cancer has remained slow. Moreover, the intensity of surveillance strategies remains to be elucidated. The objective of this study was to determine the population-based intensity of surveillance strategy among patients diagnosed with localized prostate cancer who undergo watchful waiting/active surveillance and those who receive active treatment.Linked Surveillance, Epidemiology, and End Results (SEER)-Medicare data were used to identify men diagnosed with prostate cancer from 2004 to 2007 who were followed until December 31, 2009. Bivariate and multivariate regression analyses were used to quantify the use of prostate-specific antigen tests, office visits, and second prostate biopsies within 2 years of diagnosis.Compared with patients who were receiving active treatment, those who were undergoing watchful waiting/active surveillance were less likely to receive prostate-specific antigen testing and to attend office visits within the 2 years after diagnosis (P .01). Of the 3656 patients who were undergoing watchful waiting/active surveillance, only 166 (4.5%) were on active surveillance (according to the authors' a priori definition), although the number increased over the last 2 years of the study (hazard ratio, 2.18; 95% confidence interval, 1.28-3.71; P .01). Limitations of the study included data limited to men aged 65 years or older and the lack of ability to discern between watchful waiting and active surveillance.Active surveillance is underused, and there is uncertainty regarding the quality of surveillance for patients who undergo watchful waiting/active surveillance. Further research is needed into qualitatively describing the contributing factors that drive decision-making recommendations as well as improved surveillance measures for patients with prostate cancer.

BACKGROUND Cisplatin-based combination chemotherapy for patients with advanced transitional cell carcinoma (TCC) of the urothelium has limitations, and new therapies need to be evaluated. METHODS Ifosfamide 1.0 gm/m2 on Days 1–4 and paclitaxel 135 mg/m2 by 24-hour infusion on Day 4 were administered to 26 patients with locally unresectable or metastatic TCC. Cycles were repeated every 21 days for a maximum of 6 cycles; dose escalation was dependent on whether Grade 3 or 4 toxicities occurred. RESULTS There were 24 males and 2 females, with a median age of 66 years and a median Eastern Cooperative Oncology Group performance status of 0. The median number of cycles administered was 3. Twelve patients had Grade 3 or 4 hematologic toxicities, including 1 patient who died of a gastrointestinal hemorrhage while pancytopenic. There were no episodes of neutropenic fever. Two patients each had a complete response (CR) that lasted 5 and 28 months, respectively (response rate: 15%; 95% CI: 2–45%), among the 13 patients who had received prior chemotherapy. Of the 13 patients without prior chemotherapy, there were 3 with complete responses and 1 with a partial response ranging from 8 to 25+ months (RR: 30.7%; 95% CI: 9–61%). CONCLUSIONS The combination of ifosfamide and paclitaxel is well tolerated and can produce objective responses in patients who are chemonaive or have had prior therapy. For previously untreated patients, the addition of ifosfamide does not appear to result in a better response rate than single agent paclitaxel; and for previously treated patients, the addition of paclitaxel does not appear to result in a better response rate than single agent ifosfamide. Cancer 1999;86:514–8. © 1999 American Cancer Society.

BACKGROUND Patients with relapsed germ cell cancer (GCT) have a poor prognosis when treated solely with conventional chemotherapy; high dose chemotherapy with autologous bone marrow rescue (ABMR) has shown curative potential in patients with relapsed and refractory GCT. This protocol was designed to incorporate high dose therapy with initial salvage therapy. METHODS Twenty-three patients in the first relapse of GCT received two cycles of conventional dose cisplatin-based therapy (either vinblastine, ifosfamide and cisplatin [VeIP] or cisplatin, vinblastine, and bleomycin) followed by carboplatin (1500-2100 mg/m2) and etoposide (1200-2250 mg/m2) given in divided doses with ABMR. RESULTS Eighteen of 23 patients completed protocol therapy including high dose therapy. Five of 23 did not undergo high dose therapy due to: insurance refusal (1); patient refusal (1); active infection (1); central nervous system metastasis (1); death on induction therapy (1). Response to two courses of conventional dose induction therapy (N = 23) was complete response (CR), 8; partial response (PR), 12; stable disease (SD), 2; and toxic death, 1. Two of five individuals who did not continue with high dose therapy are alive and progression free after conventional salvage therapy and surgery with at least 24 months of follow-up. Outcome after high dose therapy (N = 18) was CR, 9, PR, 6, SD, 1, and PD, 2. Two patients who were in PR after receiving two cycles of conventional dose therapy were converted to CR using high dose therapy. There was only one treatment-related death in this cohort, a septic death during VeIP induction therapy. There were no transplant related deaths. Of those patients completing high dose therapy, 7 of 18 (39%) survived, progression free with a median follow-up of 26 months, 2 of 18 are alive with active disease, and 9 of 18 died of recurrent disease. CONCLUSIONS Conventional dose induction therapy followed by consolidation with high dose therapy and ABMR is well tolerated and provides prolonged disease-free survival in some patients with chemosensitive relapsed germ cell cancer.

Background. Thymic carcinomas are rare tumors of the anterior mediastinum. These tumors are distinct thymic neoplasms that differ from their more common counterpart, thymoma. As opposed to thymomas, thymic carcinomas are histologically malignant neoplasms with a clinical course that tends to be much more aggressive than that of patients with thymoma. Methods. Between 1984 and 1990, five patients with thymic carcinoma treated with cisplatin-based combination chemotherapy were seen at Indiana University Hospital. These patients' diagnoses, courses, and treatments were reviewed. Results. Three patients responded (two completely) to cisplatin-based chemotherapy. Conclusions. This form of chemotherapy merits additional study in such patients, and our experience indicates that at least some will have clinically meaningful responses. The optimum regimen is unclear, but would contain cisplatin and probably should be similar to that used in germ cell tumors.

Forty-six eligible patients with metastatic breast cancer (MBC) were treated with a combination of methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) as first-line chemotherapy. Of 44 patients evaluable for response, 28 (64%) had an objective response, including seven (16%) who had a complete response. The median duration of response was 4 months (range, 0 to 38 months), and the median survival from the time of entry was 14 months (range, less than 1 to greater than 45 months). Myelosuppression was the most common dose-limiting toxicity, with 54% of patients experiencing Grade 3 or 4 leukopenia (including 28% with granulocytopenic fever and one septic death), and cumulative Grade 3 anemia occurred in 28% of patients. Grades 3 to 4 stomatitis was observed in 18% of patients. An active, although highly toxic regimen when used as first-line therapy in MBC, M-VAC has a response rate and survival duration similar to existing, less toxic combination regimens. As such, M-VAC cannot be recommended in preference to other combination chemotherapy regimens in this clinical setting.

Between 1976 and 1988, 31 patients with mediastinal nonseminomatous germ cell tumors (MNGCT) received initial cisplatin-based chemotherapy of uniform intensity. Eighteen of these patients (58%) obtained disease-free status; 11 with chemotherapy alone and seven with adjunctive surgery. Eleven have remained continuously free of disease. Two have had recurrence of teratoma and are disease-free after resection of teratoma at 12+ and 68+ months. Three patients developed recurrence of germ cell tumor. Three patients developed a hematologic malignancy. Of the 18 patients who obtained disease-free status, 15 remain alive and disease-free. Overall, 13 of the 31 patients and 24 other patients received salvage chemotherapy at Indiana University, Indianapolis, Indiana. Of these 37 patients, six obtained a disease-free status and four (11%) remain alive at 13+, 56+, 78+, and 122+ months, respectively. This series represents the largest series of patients with MNGCT ever reported. Analysis of these data and results from other recent series suggest that approximately 50% of patients with MNGCT will be cured with modern, intense cisplatin-based chemotherapy coupled with adjunctive surgery if needed.

To examine CDDP induced nephrotoxicity in patients with testicular carcinoma, we measured renal function prior to therapy and at six month intervals for twelve months in fifteen patients and twenty-four months in seven patients. CDDP was given iv at 20 mg/M2 per day for five days at three week intervals. Eight patients received three courses, four received four courses and three received more than four courses. The mean creatinine clearance +/- SD prior to treatment was 112 +/- 12 ml/min. By six months, it had decreased to 68.5 +/- ml/min (p less than 0.01) and it remained at that level. Plasma creatinine and blood urea nitrogen increased significantly. Subjects receiving other potential nephrotoxins in addition to CDDP developed a greater decrease in creatinine clearance (p less than 0.05). Proteinuria and functional tubular disturbances were not observed. Microscopic features were characterized by hydropic degeneration of the renal tubular epithelium, thickened tubular basement membranes and mild interstitial fibrosis. Electron microscopy revealed phagolysosomes filled with flocculent material. CDDP resulted in a permanant, nonspecific renal injury in our patients. Although the renal injury has remained subclinical, future courses of CDDP may lead to clinically important chronic renal failure.

Seventy-eight patients with disseminated testicular cancer were entered on a random prospective study evaluating three separate remission induction arms. Therapy with cis-diamminedichloroplatinum (20 mg/M2 for five consecutive days every three weeks for 3-4 courses) and bleomycin (30 units intravenous push weekly for 12 consecutive weeks) was constant. Patients were allocated at random to one of the following induction regimens (in combination with platinum plus bleomycin): (1) vinblastine 0.4 mg/kg every three weeks for four courses; (2) vinblastine 0.3 mg/kg every three weeks for four courses; or (3) vinblastine 0.2 mg/kg plus Adriamycin 50 mg/M2 every three weeks for four courses. All patients received maintenance therapy with vinblastine 0.3 mg/kg once a month for 20 months (total therapy two years) unless progressive disease intervened. The incidence of granulocytopenic fever and sepsis was highest with regimen 1, as 9 patients (35%) developed granulocytopenic fever requiring hospitalization and antibiotics; only 4 (15%) patients on regimen 2 developed granulocytopenic fever. No patients on regimen 2 had documented sepsis. Fifty-three patients (68%) achieved complete remission and an additional 11 patients were rendered free of disease with surgical resection of residual localized disease. Fifty-three patients (68%) remain alive and continuously free of disease from 15+ to 39+ months. There was no difference in the complete remission rate or disease-free status with the higher dosage of vinblastine (regimen 1) during remission induction therapy compared to the less toxic lower dosage of vinblastine (regimen 2). This suggests that dosage reduction of vinblastine to 0.3 mg/kg can produce equivalent therapeutic results with diminished toxicity, and we no longer recommend the 0.4 mg/kg vinblastine dosage.

Eleven male patients had germ cell tumors of the testis (7), mediastinum (3), or retroperitoneum (1) in which non-germ cell malignancies developed. Such malignant non-germ cell elements were present in the primary excisions of five patients and were subsequently found in additional resected tissue in 10 of 11 patients. In the patients who had multiple pathology specimens examined, a progression from atypia to predominant non-germ cell malignancy was often found. The authors believe these malignant elements arose within teratomatous foci, since eight of nine cases had teratoma in the primary tumor, and teratoma was found in subsequently resected tissue in one additional case. Cisplatin therapy frequently "unmasked" the non-germ cell malignant elements by destroying the more chemosensitive germ cell cancers. The prognosis was worst for five patients who developed progressive embryonal rhabdomyosarcoma: two of these patients died of local spread of tumor, whereas a third died of metastatic sarcoma. Only one patient, who had total surgical excision of rhabdomyosarcoma, survived. Other forms of sarcoma that developed within germ cell tumors did not appear to adversely affect the prognosis beyond that of teratoma. It is currently recommended, when feasible, that patients with teratoma and sarcoma undergo total surgical excision. Further treatment with cisplatin regimens, after eradication of the germ cell component, has not been helpful. The role of other forms of chemotherapy remains speculative.

Platinum combination chemotherapy will regularly produce a 70% complete response rate in testicular cancer. Many patients failing to achieve complete remission can still be rendered disease-free with surgical resection of residual localized disease. Twenty-one patients underwent resection for residual pulmonary lesions and 41 underwent lymphadenectomy for persistent retroperitoneal disease. There were no characteristic radiographic findings for fibrous tissue versus mature teratoma versus carcinoma. Although elevated HCG or AFP levels indicated the presence of carcinoma, negative HCG and AFP did not rule out such a diagnosis as 12 of 22 resected carcinoma patients were seronegative. Of 35 patients, 31 (89%) with fibrous tissue or mature teratomas and all four patients with immature teratomas have been continuously free of disease with a minimal postoperative follow-up time of six months. However, only two of 22 patients with resected carcinomas have been continuously disease-free. Post-operative chemotherapy for mature teratoma or fibrous tissue is probably not necessary. However, we feel that further aggressive chemotherapy is needed in the resected carcinoma patient with at least two courses of platinum combination chemotherapy. Surgical resection of residual disease following chemotherapy-induced cytoreduction with platinum combination chemotherapy may be therapeutic in some cases and helps to define the optimal subsequent treatment strategy.

Eighteen patients with advanced Hodgkin's disease, refractory to combination chemotherapy with nitrogen mustard, vincristine, prednisone, and procarbazine (MOPP), were treated with vinblastine, doxorubicin (Adriamycin), bleomycin, CCNU, and dacarbazine (DTIC) (VABCD). Fifteen patients had Stage IV disease and 11 had systemic symptoms. Although hematologic toxicity was considerable, there was no drug related mortality. Eight patients achieved a complete remission (CR), and five are currently in a continuous CR of five, 24, 30, 34, and 36 months duration, respectively. An additional patient had a 30-month CR and relapsed with localized lymphadenopathy and is currently disease-free following involved-field radiotherapy 46 months from initiation of VABCD. This study suggests that long-term disease-free survival and potential cure can be achieved with VABCD in MOPP-refractory Hodgkin's disease.

One hundred ninety-one patients with recurrent or metastatic squamous cell carcinoma of head and neck origin were allocated at random to chemotherapy with conventional-dose weekly intravenous methotrexate or the combination of cisplatin, vinblastine, and bleomycin. Methotrexate induced responses in 16 of 98 patients (16%), whereas 22 of 92 (24%) responded to the combination regimen (P = not significant). Remission duration (20.2 weeks methotrexate; 15.1 weeks combination) was similar on both arms, as was survival (31.4 weeks methotrexate; 29.0 weeks combination). Therapy was relatively well-tolerated on both treatment arms, although methotrexate produced more mucositis and the combination more gastrointestinal and renal toxicity. Response to chemotherapy and disease confined to the locoregional area were associated with somewhat longer survival. Combination chemotherapy as given in this study did not improve any observed parameter, and the results of treatment were poor in both arms.

The completely resected teratomatous metastases of 55 patients who had been treated with cisplatin-based combination chemotherapy for non-seminomatous germ cell tumors were reviewed to see if cellular atypia had an effect with respect to recurrent disease. The degree of atypia of the epithelial and mesenchymal elements was assessed on the basis of the cytologic features and mitotic activity. Twenty-three percent of the cases contained high-grade epithelial elements, whereas high-grade mesenchymal elements occurred in 18% of the cases; in addition there were nine cases classified as showing frankly malignant teratomatous elements. The presence of cytologically disturbing epithelial and mesenchymal elements (which, however, lacked an invasive malignant pattern) correlated with an increased incidence of recurrent teratoma compared to less atypical teratomatous elements (23% vs. 6% for epithelial elements, and 18% vs. 9% for mesenchymal elements, respectively). This difference, however, was not statistically significant (P greater than 0.05). There was no correlation between teratomatous atypia and recurrent, non-teratomatous germ cell tumor. The presence of an invasive malignant pattern did identify patients at significantly increased risk for recurrent teratoma-derived tumor. The authors conclude that cytologic atypia in the absence of invasion is not sufficient justification for altering the usual therapeutic strategies for patients with teratomatous metastases.

Thirty-three patients with advanced refractory germinal neoplasms were treated with VP-16-213 alone or in combination with cis-platinum, bleomycin, and frequently Adriamycin. All had prior chemotherapy, which in most was extensive. There were 14 complete and 15 partial remissions. Five of the patients with partial remission were rendered disease free by resection of residual tumor. Eleven remain disease free from 6+--23+ months. Toxicity was considerable. One-third were hospitalized for fever and granulocytopenia and four had life-threatening thrombocytopenia. There was one drug-related death. VP-16 is an active drug in germinal neoplasms. It appears to be an important component of "salvage" regimens for refractory patients, but severe toxicity may ensue.

From July 1973, to March 1978, 139 patients with disseminated germinal neoplasms were treated with a variety of combination chemotherapy regimens. Twenty-one patients (15.1%) exhibited evidence of brain metastases at some time during their course. Central nervous system spread occurred somewhat more frequently in patients with choriocarcinoma and yolk sac histologies, although all types were at risk. This was a major cause of morbidity and mortality. However, central nervous system spread almost always occurred in patients with systemic relapse and thus did not affect overall survival. We have yet to identify a subgroup who potentially could benefit from prophylactic central nervous system therapy.