HIV-discordant and concordant HIV-positive male couples' recommendations for how an eHealth HIV prevention toolkit for concordant HIV-negative male couples could be improved to meet their specific needs.

A number of HIV prevention interventions for male couples are in the pipeline for development as few evidence-based ones exist. Among these projects, none include all three groups of male couples (concordant HIV-negative, HIV-discordant, and concordant HIV-positive) as their target population, and only two are eHealth-based. The present qualitative study sought to assess whether one of the eHealth HIV prevention interventions for concordant HIV-negative male couples - called MCAP - could be adapted to meet the relationship and HIV prevention needs of HIV-discordant and HIV-positive male couples. Data for this study are drawn from in-person, individual-level interviews conducted with a convenience sample of 10 HIV-discordant male couples (n = 20) and 8 HIV-positive male couples (n = 16) from the Miami-Fort Lauderdale metro area in 2016. Thematic analysis was conducted to identify patterns (themes) of partners' thoughts about the toolkit, including how they perceived it could be improved for their own relationship and other couple's relationships. Two themes emerged from analysis of the qualitative data suggesting how the participants wanted the toolkit to be improved to meet their needs. Specifically, participants recommended for the toolkit to include guidance about integrating the use of biomedical HIV prevention strategies into couple's relationships, as well as for how partners can best take care of each other and further protect themselves from HIV and/or other STIs (Prevention Guidance). In addition, participants requested for the concept of sexual agreements to be broadened to include other aspects they deemed to be important in their life (e.g., mental health, exercise and nutrition) (Holistic agreements). Findings from the present study illuminate the ways in which MCAP would need to be adapted for these two groups of male couples in order to meet the needs for all three groups of male couples in the U.S. in a future iteration of this intervention.

Pegylated liposomal doxorubicin plus carboplatin in patients with metastatic breast cancer: a phase II study.

BACKGROUND: We determined the objective response rates produced by pegylated liposomal doxorubicin (PLD) plus carboplatin with/without trastuzumab (Herceptin). PATIENTS AND METHODS: Patients with measurable disease were stratified by taxane treatment history and human epidermal growth factor receptor-2 status. TREATMENT: PLD 30 mg/m(2) followed by carboplatin, day 1 of each 28-day cycle; human epidermal growth factor receptor-2 (HER2)-positive patients also received trastuzumab. RESULTS: Arm 1 received PLD plus carboplatin (N = 41 arm 1a, taxane naive; N = 42 arm 1b, taxane pretreated); Arm 2 patients received PLD plus carboplatin + Herceptin (N = 46). Overall response rates: 31%, 31%, and 56%, respectively. Median overall survival durations were not reached in arm 1a and were 13 and 33 months for arms 1b and 2. Median progression-free survival: 8, 5, 10 months, respectively. Grades 3-4 treatment-related toxic effects for arms 1a, 1b, 2, respectively, were neutropenia 22%, 31%, 35%; thrombocytopenia 34%, 26%, 17%; and fatigue 2%, 14%, 13%. CONCLUSIONS: PLD plus carboplatin has moderate antitumor activity and excellent tolerability. Herceptin and PLD plus carboplatin in HER2-positive patients have antitumor activity without significant cardiac toxicity. Toxicity results suggest that PLD can be combined with Herceptin with minimal cardiac toxicity.

Sunitinib malate for metastatic castration-resistant prostate cancer following docetaxel-based chemotherapy.

BACKGROUND: Systemic therapy options are limited for metastatic castration-resistant prostate cancer (CRPC) patients who progress following docetaxel (Taxotere). This phase II trial evaluated sunitinib malate in patients with progressing metastatic CRPC following prior docetaxel. PATIENTS AND METHODS: Patients with metastatic CRPC progressing following one to two chemotherapy regimens including docetaxel were included. The primary end point was progression-free survival (PFS) per radiographic and clinical evaluations. Oral sunitinib was administered 50 mg/day 4-weeks on followed by 2-weeks off per cycle up to a maximum of eight cycles or until clinical progression or intolerable toxicity. RESULTS: Thirty-six patients with a median age of 69.5 years were accrued. The median PFS was 19.4 weeks with a 12-week PFS of 75.8%. Four patients (12.1%) had a > or =50% prostate-specific antigen (PSA) decline and seven (21.2%) had a > or =30% PSA decline. Two of 18 patients (11.1%) with measurable disease demonstrated 30% declines by RECIST and eight (44.4%) displayed some shrinkage. A decline in pain score > or =2 points occurred in 13.6% of 22 assessable patients. Drug discontinuation due to toxic effects occurred in 52.8% of patients. CONCLUSION: Sunitinib malate demonstrated promising activity in metastatic CRPC progressing after prior docetaxel.

Phase II trial of docetaxel and oxaliplatin in patients with advanced gastric cancer and/or adenocarcinoma of the gastroesophageal junction.

BACKGROUND: Platinum-based chemotherapy is the standard treatment for advanced gastric cancer (GC). This trial explored the efficacy and tolerability of combined docetaxel (Taxotere) + oxaliplatin (DOCOX) in GC patients. PATIENTS AND METHODS: Patients with untreated stage IV GC or adenocarcinoma of the gastroesophageal junction (AGEJ) received docetaxel 60 mg/m(2) followed by oxaliplatin 130 mg/m(2) on day 1 of each 21-day cycle until progression or unacceptable toxicity. The primary end points were response rate (RR), toxicity, progression-free survival (PFS), and overall survival (OS). RESULTS: Baseline characteristics (N = 71): median age 59 years, 72% male, 51% esophagogastric junction cancer, and Eastern Cooperative Oncology Group performance status of zero, one, two were 42%, 51%, 7%, respectively. The median number of cycles was 6 (range, 1-19). Grades 3-4 toxic effects: neutropenia (70%); vomiting (17%); nausea (16%); dehydration, fatigue, or diarrhea (13%, each); and thrombocytopenia or febrile neutropenia (7%, each). Sixty-six patients completed >/=2 cycles. The RR was 36% with 25 partial response (PR) and no complete responses (CRs); stable disease (SD) was 49%. Clinical benefit rate (CBR = CR + PR + SD >/=6 months) was 40%; median PFS was 4.3 months, and OS was 8.5 months. CONCLUSIONS: DOCOX produced manageable toxicity in patients with advanced GC and AGEJ. The confirmed RR of 36%, CBR of 40%, and median survival of 8.5 months are encouraging and comparable to standard front-line regimens.

Tumor-cell DNA content predicts outcome in children and adolescents with clinical group III embryonal rhabdomyosarcoma. The Intergroup Rhabdomyosarcoma Study Committee of the Children's Cancer Group and the Pediatric Oncology Group.

PURPOSE: The prognostic value of tumor-cell DNA content (ploidy) was evaluated in children with unresectable, nonmetastic rhabdomyosarcoma of embryonal histology. PATIENTS AND METHODS: Flow-cytometric techniques were used to estimate the ploidy of tumor specimens from 34 patients with embryonal rhabdomyosarcoma who were enrolled in the intergroup rhabdomyosarcoma study III (IRS III) from 1985 to 1991. Tumors were classified as diploid or hyperdiploid (DNA content, 1.1 to 1.8 times that of normal diploid cells). The influence of ploidy on clinical outcome was assessed by the Kaplan-Meier technique and Cox regression analysis with stepwise selection. RESULTS: Twelve of the tumor specimens were diploid and 22 were hyperdiploid. The patient groups defined by diploid or hyperdiploid tumors had similar presenting characteristics (eg, age, tumor size, and anatomic site). Significantly more children with hyperdiploid tumors achieved a complete response than did children with diploid tumors (85% v 42%; P = .01). The probability of progression-free survival at 5 years (+/- SE) was 91% +/- 6% for the hyperdiploid group, compared with 17% +/- 11% for the diploid group (P < .001). Hyperdiploidy was also associated with a significantly higher overall survival rate at 5 years: 96% +/- 4% versus 50% +/- 14% (P = .004). Ploidy retained its prognostic significance after adjustment for tumor site in the Cox regression model. CONCLUSION: Tumor-cell ploidy strongly correlates with outcome in children with nonmetastic, unresectable embryonal rhabdomyosarcoma. The two biologically distinct groups identified by this measure would benefit from further refinements in risk-directed therapy.

Estrogen replacement therapy after localized breast cancer: clinical outcome of 319 women followed prospectively.

PURPOSE: To determine whether estrogen replacement therapy (ERT) alters the development of new or recurrent breast cancer in women previously treated for localized breast cancer. PATIENTS AND METHODS: Potential participants (n = 319) in a trial of ERT after breast cancer were observed prospectively for at least 2 years whether they enrolled onto the randomized trial or not. Of 319 women, 39 were given estrogen and 280 were not given hormones. Tumor size, number of lymph nodes, estrogen receptors, menopausal status at diagnosis, and disease-free interval at the initiation of the observation period were comparable for the trial participants (n = 62) versus nonparticipants (n = 257) and for women on ERT (n = 39) versus controls (n = 280). Cancer events were ascertained for both groups. RESULTS: Patient and disease characteristics were comparable for the trial participants versus nonparticipants, as well as for the women on ERT versus the controls. One patient in the ERT group developed a new lobular estrogen receptor-positive breast cancer 72 months after the diagnosis of a ductal estrogen receptor-negative breast cancer and 27 months after initiation of ERT. In the control group, there were 20 cancer events: 14 patients developed new or recurrent breast cancer at a median time of 139.5 months after diagnosis and six patients developed other cancers at a median time of 122 months. CONCLUSION: ERT does not seem to increase breast cancer events in this subset of patients previously treated for localized breast cancer. Results of randomized trials are needed before any changes in current standards of care can be proposed.

Impact of selection process on response rate and long-term survival of potential high-dose chemotherapy candidates treated with standard-dose doxorubicin-containing chemotherapy in patients with metastatic breast cancer.

PURPOSE: Most of the data about high-dose chemotherapy (HDCT) for metastatic breast cancer are derived from phase II studies. The interpretation of these data depends on comparisons with data from properly selected historical control patients treated with standard therapy under similar circumstances. We report the long-term results of patients with metastatic breast cancer who were eligible for HDCT but were treated with doxorubicin-containing standard-dose chemotherapy. PATIENTS AND METHODS: Prospectively collected data from 18 successive doxorubicin-containing protocols for the treatment of metastatic breast cancer were evaluated. Using common eligibility criteria for HDCT, we identified patients who would have been candidates for HDCT. We analyzed response rates, progression-free survival (PFS), and overall survival (OS) for all patients, potential HDCT candidates, and noncandidates. RESULTS: A total of 1,581 patients was enrolled onto the 18 studies. Six hundred forty-five were HDCT candidates, and 936 were noncandidates. The complete response rate was 27% for HDCT candidates and 7% for noncandidates; median PFS was 16 and 8 months and median OS was 30 and 17 months, respectively. Survival rates for HDCT candidates and noncandidates, respectively, were 21% and 6% at 5 years and 7% and 2% at 10 years. CONCLUSION: This study suggests that encouraging results of single-arm trials of HDCT could partially be due to selection of patients with better prognoses and further stresses the importance of completing ongoing randomized trials of HDCT to assess the relative efficacy of HDCT in patients with metastatic breast cancer.

Long-term results of combined-modality therapy for locally advanced breast cancer with ipsilateral supraclavicular metastases: The University of Texas M.D. Anderson Cancer Center experience.

PURPOSE: To determine outcomes in local-regional control, disease-free survival, and overall survival in patients with locally advanced breast cancer (LABC) who present with ipsilateral supraclavicular metastases and who are treated with combined-modality therapy. PATIENTS AND METHODS: Seventy patients with regional stage IV LABC, which is defined by our institution as LABC with ipsilateral supraclavicular adenopathy without evidence of distant disease, received treatment on three prospective trials of neoadjuvant chemotherapy. All patients received neoadjuvant chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil, or cyclophosphamide, doxorubicin, vincristine, and prednisone. Patients then received local therapy that consisted of either total mastectomy and axillary lymph node dissection (ALND) or segmental mastectomy and ALND before or after irradiation. Patients with no response to neoadjuvant chemotherapy were treated with surgery and/or radiotherapy. After completion of local therapy, chemotherapy was continued for four to 15 cycles, followed by radiotherapy. Patients older than 50 years who had estrogen receptor-positive tumors received tamoxifen for 5 years. RESULTS: Median follow-up was 11.6 years (range, 4.8 to 22.6 years). Disease-free survival rates at 5 and 10 years were 34% and 32%, respectively. The median disease-free survival was 1.9 years. Overall survival rates at 5 and 10 years were 41% and 31%, respectively. The median overall survival was 3.5 years. The overall response rate (partial and complete responses) to induction chemotherapy was 89%. No treatment-related deaths occurred. CONCLUSION: Patients with ipsilateral supraclavicular metastases but no other evidence of distant metastases warrant therapy administered with curative intent, ie, combined-modality therapy consisting of chemotherapy, surgery, and radiotherapy. Patients with ipsilateral supraclavicular metastases should be included in the stage IIIB category of the tumor-node-metastasis classification because their clinical course and prognosis are similar to those of patients with stage IIIB LABC.

Ewing's sarcoma of soft tissues in childhood: a report from the Intergroup Rhabdomyosarcoma Study, 1972 to 1991.

PURPOSE: One hundred thirty of 2,792 patients (5%) registered on three Intergroup Rhabdomyosarcoma Study clinical trials (IRS-I, -II, and -III) from 1972 to 1991 had an extraosseous Ewing's sarcoma (EOE). We report here the results of multimodality therapy for this tumor. PATIENTS AND METHODS: The 130 patients were less than 21 years of age; 70 (54%) were males. Primary tumor sites were on the trunk in 41 patients, an extremity in 34, the head/neck in 23, the retroperitoneum/pelvis in 21, and other sites in 11. One hundred fourteen patients had no metastases at diagnosis. In 21 patients, the tumor was completely resected; in 30, the localized or regional tumor was grossly resected, and in 63 patients, grossly visible sarcoma was left behind. Sixteen patients (12%) had distant metastases at diagnosis. All patients were given multiagent chemotherapy and most received irradiation (XRT); none were treated with bone marrow transplantation. RESULTS: One hundred seven patients (82%) achieved a complete response. At 10 years, 62%, 61%, and 77% of the patients were alive after treatment on IRS-I, IRS-II, or IRS-III therapeutic protocols, respectively, similar to figures obtained in all IRS patients. At last follow-up evaluation, 42 patients had died of progressive tumor and one of infection. Survival at 10 years was most likely for patients with tumor that arose in the head and neck, extremities, and trunk, and for those who underwent grossly complete tumor removal before initiation of chemotherapy. For patients with localized, gross residual tumor, adding doxorubicin (DOX) to the combination of vincristine, dactinomycin, cyclophosphamide (VAC), and XRT did not significantly improve survival in 39 patients (62% alive at 10 years) compared with that of 24 patients treated with VAC and XRT without DOX (65% alive at 10 years, P = .93). CONCLUSION: This series indicated that EOE in children is similar to rhabdomyosarcoma (RMS) in its response to multimodal treatment. No benefit was apparent from the addition of DOX to VAC chemotherapy in patients with gross residual EOE.

Prospective evaluation of paclitaxel versus combination chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide as neoadjuvant therapy in patients with operable breast cancer.

PURPOSE: To compare prospectively the antitumor activity of single-agent paclitaxel to the three-drug combination of fluorouracil, doxorubicin, and cyclophosphamide (FAC) as neoadjuvant therapy in patients with operable breast cancer. PATIENTS AND METHODS: Patients with T1-3N0-1M0 disease were randomized to receive either paclitaxel (250 mg/m(2)) as 24-hour infusion or FAC in standard doses at every-3-week intervals. Each patient was treated with four cycles of preoperative chemotherapy. Clinical response and extent of residual disease in the breast and lymph nodes was assessed after four cycles of induction chemotherapy. RESULTS: A total of 174 patients were registered, and 87 were randomized to each arm of the study. Clinical response, ie, complete and partial responses, was similar in both arms of the study. Three patients in the FAC arm and one patient in the paclitaxel subgroup had progressive disease. The extent of residual disease by intent-to-treat analysis at the time of surgery was similar between the two arms of the study. CONCLUSION: The results of this prospective study demonstrated that single-agent paclitaxel as neoadjuvant therapy has significant antitumor activity, and this was clinically comparable to FAC. Similar fractions of patients had clinical complete and partial responses, and very few patients had no response to either therapy. The value of alternate non-cross-resistant therapies as used in this protocol on the clinical course of this disease would require longer follow-up.

Sequential versus concurrent paclitaxel and carboplatin for the treatment of advanced non-small cell lung cancer in elderly patients and patients with poor performance status: results of two Phase II, multicenter trials.

The primary objective of these trials was to determine the 1-year survival of advanced non-small cell lung cancer (ANSCLC) patients (> or =70 years with PS 0-2 or > or =18 years with PS 2) receiving sequential paclitaxel and carboplatin (P --> C) or concurrent P + C. The secondary objectives were assessment of toxicities and quality of life. A total of 121 patients with NSCLC were treated. P--> C patients received paclitaxel (80 mg/m(2)) weekly x 3, followed by 1 week of rest; these 4-week cycles were repeated until relapse. At relapse, patients received carboplatin (AUC = 5, IV) on Day 1 of each 3-week cycle until evidence of further progression or lack of improvement. P + C patients received paclitaxel (80 mg/m(2)) and carboplatin (AUC = 2), weekly x 3, followed by 1 week of rest, until relapse. Patients in both studies were premedicated prior to paclitaxel administration. Sequential P + C resulted in a median survival of 8.2 months (range: <1-18.8) and P + C patients had a median survival of 9.2 months (range: <1-22.0). In both groups (P--> C) and P + C), the 1-year survival was 31%. For patients treated sequentially, treatment-related AEs (TRAE, > or =Grade 3) included fatigue (7%), neuropathy (5%), and leukopenia and diarrhea (3%, each). Grade 4 AEs were limited to neutropenia, febrile neutropenia, and sepsis (1 episode each). For patients receiving concurrent P + C, TRAE included neutropenia and leukopenia (15%, each) and shortness of breath and bilateral bone pain (10%, each). Leukopenia (n = 2) and neutropenia (n = 1) were the only Grade 4 events reported. The analysis of quality of life (QOL) questionnaires indicated that there were no obvious differences between treatment groups during the study. These drugs and treatment schema were well-tolerated when administered in the community setting and resulted in survival rates that were similar to what is reported in the literature with combination therapy administered to "high risk" patients. Finding the optimal chemotherapy regimen, that can be tolerated, remains a challenge in elderly patients.

Impact of patient characteristics on treatment outcome: anthracycline resistance.

In the treatment of breast cancer, anthracycline-containing combinations are frequently used as adjuvant therapy or to treat patients with metastatic disease. However, most patients with metastatic disease who are treated with these combinations develop progressive disease and a significant proportion of patients, after receiving anthracycline-containing adjuvant therapy, experience recurrent disease. Patients who develop recurrent disease while receiving adjuvant therapy and those whose metastatic disease progresses without an objective response while on treatment to control the disease, are among those defined as having primary refractory disease. These patients have a poor prognosis. In other patients whose breast cancer is treated with anthracycline-containing combinations, defining the degree of resistance requires careful consideration of the type of response to therapy (complete response, partial response or no change in disease status) the duration of response and, for patients in the adjuvant setting, the length of the disease-free interval.

Phase II trial of single-agent weekly docetaxel in hormone-refractory, symptomatic, metastatic carcinoma of the prostate.

The purpose of this study was to assess the efficacy of weekly administration of docetaxel as a single agent in patients with hormone-refractory, symptomatic, metastatic prostate cancer with respect to symptom palliation, tumor response, time to progression, and survival. Sixty men with progressive metastatic prostate cancer that had progressed on at least one hormonal regimen were enrolled in this multicenter phase II study. Twenty-one percent of patients had received prior palliative radiotherapy, and 25% had received prior chemotherapy for hormone-refractory disease. Patients were scheduled to receive three 8-week cycles of docetaxel (36 mg/m(2) on days 1, 8, 15, 22, 29, and 36) with 2-week intervals between cycles. The docetaxel dose could be decreased in the event of toxicity, but no dose escalation was permitted. A > or =50% decrease in serum prostate-specific antigen (PSA) levels from baseline with stabilization or improvement of performance status lasting 2 months or longer occurred in 24 (41%) patients, of whom 16 (27%) had a > or =80% decrease for 2 months or more. The median time to progression for all patients was 5.1 months (range, 0.9 to 18.2 months). The estimated median time to progression for patients who had and those who did not have a > or =50% reduction in serum PSA level with stable or improved performance status was 6.65 and 4.3 months, respectively. The median overall survival was 9.4 months (range, 1.6 to 18.2 months). Treatment toxicity was considered acceptable. Single-agent docetaxel at 36 mg/m(2) weekly was associated with a PSA response rate of 41%, increased time to progression and survival, and minimal myelosuppression in patients with hormone-refractory metastatic prostate cancer.

Prospective randomized trial of paclitaxel alone versus 5-fluorouracil/doxorubicin/cyclophosphamide as induction therapy in patients with operable breast cancer.

The objective of this study was to compare the antitumor activity of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) with that of the 5-fluorouracil/doxorubicin/cyclophosphamide (FAC) combination by evaluating the extent of residual disease in the breast and regional lymph nodes of patients with breast cancer following four cycles of induction chemotherapy. Patients with histologically confirmed invasive but noninflammatory carcinoma of the breast stages T2-3, N0-1, M0 were eligible to enter the study. Patients were treated with four cycles of either FAC or single-agent paclitaxel before local therapy. Following local therapy, treatment of the two arms was identical. Of 104 operable breast cancer patients who were treated with either regimen, 78 were evaluable for response to preoperative chemotherapy and had undergone local therapy. Age, TNM classification, and estrogen receptor status of the patients were similar in the two groups. Following induction chemotherapy, the extent of disease in the breast and the distribution and number of positive nodes were similar between the two treatment arms. Disease progressed in two patients in the FAC arm and in none in the paclitaxel arm during the induction phase of therapy. A higher fraction of patients had neutropenic fever during the paclitaxel treatment. Initial data from this ongoing randomized study show that paclitaxel alone has comparable anticancer activity with FAC in patients with early breast cancer. The degree of cytoreduction was similar with both induction therapies.

Hyperfractionated radiation in children with rhabdomyosarcoma--results of an Intergroup Rhabdomyosarcoma Pilot Study.

PURPOSE: The Intergroup Rhabdomyosarcoma Study (IRS) Group initiated a pilot study (IRS IV-P) of hyperfractionated radiation (HF XRT) with chemotherapy to test the feasibility and toxicity of this combined modality approach in children with localized but nonresected (group III) and metastatic (group IV) rhabdomyosarcoma. METHODS AND MATERIALS: Using the linear quadratic equation, and an alpha/beta ratio of 10 Gy for acute reacting tumor effect and 3 Gy for late reacting normal tissue effect, a HF XRT protocol was developed giving a total radiation dose of 59.4 Gy, in 1.10 Gy fractions, twice daily at 6-8 h intervals. All patients received chemotherapy in addition to irradiation. The radiation scheme was calculated to increase the biologically effective dose to the tumor by 10% without increasing late effects, when compared to a conventional schedule of 50.4 Gy in 1.8 Gy daily fractions. This protocol also was predicted to cause an increase in acute normal tissue effects. RESULTS: Four hundred forty-nine children age 21 years and younger were eligible for the hyperfractionated radiation study of whom 297 had Group III disease and 152 had Group IV disease. A total of 117 patients were excluded from the feasibility and toxicity analysis because of progressive disease or death prior to scheduled irradiation, surgical resection, major protocol violation, treatment with brachytherapy, or missing data. Thus, 332 children were evaluable for the HF XRT protocol. Twenty-eight of the 332 (8%) were given conventional radiation because of physician preference or young age. Twenty of the 332 (6%) were not irradiated because of young age, anesthesia, or transportation problems. All nonirradiated children were < or = 3 years of age. Thus, 284 children, 86% of the evaluable population, received HF XRT. The radiation dose, number of fractions, number of days, and interfractional interval were scored as appropriate in 93% of cases. Review of radiation portals revealed that in 230 of 284 cases (81%) the radiation fields were appropriate, as per protocol. Thus, the HF XRT was feasible treatment in a multiinstitutional study. Analysis of toxicity revealed that 152 of 204 (75%) of Group III and 52 of 80 (65%) of Group IV patients experienced severe or life-threatening toxicity, explained by the addition of chemotherapy with the radiation. The majority of this toxicity was hematopoietic. Observed organ toxicity, which was potentially explained by the radiation treatment, was greatest at the end of radiation, and improved at the 6-week and 3-month evaluation periods. There were no deaths attributed to radiation toxicity and no instance of toxicity that required alteration of the radiation protocol. Thus, the treatment was not associated with toxicity that was considered excessive or unusual. CONCLUSION: The IRS IV-P study confirms that HF XRT combined with chemotherapy is both feasible and tolerable in children with rhabdomyosarcoma. A prospective randomized trial is underway to test its efficacy as compared to conventional radiation among children also receiving concurrent chemotherapy for rhabdomyosarcoma.

Rhabdomyosarcomas with intermediate-filament inclusions and features of rhabdoid tumors. Light microscopic and immunohistochemical study.

A group of 27 rhabdomyosarcomas (RMS) whose histology showed abundant cells containing cytoplasmic intermediate-filament globular inclusions resembling those seen in rhabdoid tumors has been identified among Inter-group Rhabdomyosarcoma Study (IRS) I-III patients (less than 1%). Their histologic subtype was embryonal RMS in 22 and alveolar RMS in 5. One-half of tumors occurred in deep muscles of the extremities, retroperitoneum, or in the pelvis. Immunohistochemical analysis of 12 cases showed the inclusions to be vimentin or desmin positive. Anti-muscle-specific actin antibodies were positive in the cytoplasm of 11 cases, but not in the site of the intermediate-filament inclusions. Seven poorly differentiated neoplasms closely resembled rhabdoid tumors and possessed large nucleoli in most cells along with cytoplasmic inclusions. In contrast to true rhabdoid tumors, their nuclear chromatin was usually coarse. Immunohistochemistry proved useful in distinguishing tumors with early myoblastic differentiation. A positive anti-desmin, when confined to the cytoplasmic inclusions only, should be complemented with other muscle-specific antibodies, especially anti-muscle actin to separate RMS from rhabdoid tumors. The statistical analysis was limited by the small number of cases, but there was no statistical difference in survival when this group of RMS was compared with 996 IRS-II patients as a whole. The distinction of RMS with abundant intermediate-filament inclusions from rhabdoid tumors is of clinical importance because patients with true rhabdoid tumors have a highly unfavorable prognosis.

Childhood rhabdomyosarcoma with anaplastic (pleomorphic) features. A report of the Intergroup Rhabdomyosarcoma Study.

The pleomorphic subtype of rhabdomyosarcoma (RMS) is now rarely diagnosed in both children and adults. Most cases previously called pleomorphic RMS are probably diagnosed as something else, most often embryonal RMS in children and malignant fibrous histiocytoma in adults. To analyze the concept of pleomorphic RMS in children, we reviewed the tumors of patients entered on the Inter-group Rhabdomyosarcoma Study (IRS I, II, and III). The presence of cells with lobated, hyperchromatic nuclei at least three times larger than the common tumor cell population (anaplastic cells) was selected as the main criterion. Of about 3,000 cases, 110 showed these types of cells, had sufficient histologic material, and had available follow-up data. These tumors were divided into two subgroups: Subgroup I tumors contained only scattered anaplastic cells, and tumors with foci or large sheets of anaplastic cells were classified as subgroup II. Besides the anaplastic-pleomorphic areas, most of these tumors had distinctive features of embryonal RMS (105 cases) and rarely had characteristics of alveolar RMS (five cases). The age distribution of these patients did not differ significantly from those whose tumors did not show the anaplastic features, the average being 6 years and the median 4 years. Lower extremity, retroperitoneum, and the head and neck region were the most common primary tumor sites. The 5-year survival rate was 60% for subgroup I tumors and 45% for subgroup II tumors compared with the survival rate of 68% for 482 IRS II embryonal RMS cases with no anaplastic-pleomorphic features. The lower survival rate for patients in subgroup II was statistically significant (p = 0.004) and similar to the unfavorable survival of patients with alveolar RMS and undifferentiated sarcoma. Because anaplastic cells are seen in many soft tissue sarcomas and in both embryonal and alveolar RMS in children, this feature is not sufficiently unusual to separate a pleomorphic subtype of RMS. The presence of anaplastic cells in aggregates or diffuse sheets throughout the tumor, however, portends a poor survival for these patients.

Spindle cell variants of embryonal rhabdomyosarcoma in the paratesticular region. A report of the Intergroup Rhabdomyosarcoma Study.

We reviewed 173 cases of paratesticular rhabdomyosarcoma (RMS) of Intergroup Rhabdomyosarcoma Studies (IRS)-I, -II, and -III for evaluation of possible histological factors that might account for the good prognosis of these patients. Almost all cases (161 of 173 cases, 93.1%) occurring in this site were of embryonal histology. A spindle-cell subtype of embryonal RMS was identified that presented a storiform growth pattern with abundant collagen between the tumor cells in most cases. Other tumors of this subtype showed an arrangement of tumor cells in bundles with a low to moderate amount of collagen, resembling a leiomyosarcoma. The other embryonal RMS in this site had the classical embryonal cytology. The spindle-cell subtype was highly differentiated by immunohistochemistry and electron microscopy. Lymph node metastasis was found in seven of 43 patients (16.3%) with a RMS of spindle-cell subtype, compared with 40 of 112 patients (35.7%) with RMS of non-spindle-cell type. Clinical data from patients with spindle-cell subtypes of the paratesticular lesions revealed that they almost always had an association with clinical groups of limited disease (32 patients, 74.4%, with Group I; 10 patients, 23.3%, with Group II disease) and a significantly better prognosis (95.5% survival at 5 years) when compared with patients with the classic embryonal variant of RMS (80% survival at 5 years, p < 0.035). The incidence and anatomic distribution of this spindle cell subtype of embryonal RMS was estimated on 800 randomly selected patients from IRS-II. It was found in the head and neck, extremities, orbit, and some other sites, but 30.6% were located in the paratesticular area. Patients with spindle cell RMS of nonparatesticular sites usually had more extensive disease compared with patients having paratesticular lesions; two thirds of the cases had gross residual tumor after surgery or metastatic tumor at diagnosis. We conclude that spindle-cell RMS is a subtype of embryonal RMS with a very favorable prognosis. The site factor of the paratesticular localization may allow earlier diagnosis of the spindle-cell lesions compared with other sites. Other unknown factors may also play a role.

The efficacy of chemotherapy with docetaxel and paclitaxel in anthracycline-resistant breast cancer (Review).

This review was performed to determine the efficacy of commonly used cytotoxic agents in the management of anthracycline-resistant breast cancer, using a stringent and uniform definition of drug resistance. We reviewed the reports of second- and third-line chemotherapy after anthracycline-containing regimens published over the last two decades. Only studies with sufficient information on the timing of progressive disease in relation to anthracycline therapy were considered. All assessable studies were reviewed individually, and the data obtained with taxanes in anthracycline-resistant breast cancer were also pooled to estimate the activity. The great majority of published studies on second- and third-line chemotherapy lack useful information about anthracycline resistance. Among the few studies with sufficient information about anthracycline resistance, several definitions were used. We reanalyzed those reports utilizing a uniform definition of anthracycline resistance: progression while receiving an anthracycline. Only studies using paclitaxel or docetaxel reported an activity in this anthracycline-resistant population, allowing a response rate between 6-50% and 32-57% for both agents respectively. The activity of other cytotoxic agents in anthracycline-resistant breast cancer could not be determined because a lack of accurate data using the stringent definition. Both paclitaxel and docetaxel have substantial antitumor activity in patients with clearly defined anthracycline-resistant breast cancer. The activity of other cytotoxic agents in this group of patients remains to be established.

Rhabdoid tumors of soft tissues: a clinicopathologic study of 26 cases enrolled on the Intergroup Rhabdomyosarcoma Study.

Twenty-six cases of malignant soft tissue tumors with features similar to renal rhabdoid tumors were identified among approximately 3,000 childhood sarcomas entered on Intergroup Rhabdomyosarcoma Studies I-III. The tumors consisted of polygonal cells with vesicular nuclei and prominent nucleoli and cytoplasmic intermediate filament inclusions as identified by electron microscopy and immunohistochemistry. The growth pattern was predominantly solid or solid-trabecular. Immunohistochemistry showed vimentin, wide spectrum keratin, and epithelial membrane antigen to be the most consistent antigenic phenotypes. Eleven patients were infants less than 1 year of age. The tumors affected predominantly soft tissues of proximal extremities, trunk, and retroperitoneum/pelvis/abdomen. Nineteen patients died within 1 to 82 months (median, 6 months) from the start of treatment. Five patients have survived the disease for 2 to 13 years. When compared with the survival analysis of 991 Intergroup Rhabdomyosarcoma Study II patients, it was obvious that this group of tumors fares very poorly (P less than .001). The tumor belongs to the group of soft tissue neoplasms showing mesenchymal and subtle epithelial differentiation, similar to epithelioid sarcoma. Because of its identifiable histology, site and age distribution, and poor outcome, it warrants a status as an independent entity.