bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase I trial of paclitaxel in children with refractory solid tumors: a Pediatric Oncology Group Study.
Authors: Hurwitz C A , Relling M V , Weitman S D , Ravindranath Y , Vietti T J , Strother D R , Ragab A H , Pratt C B
Published: February 2017

PURPOSE

A phase I study was performed to describe the principal toxicities and identify the maximum-tolerated dose (MTD) of Taxol (paclitaxel; Bristol-Myers Squibb Co, Wallingford, CT) in children with therapy-resistant solid tumors. Additionally, the pharmacokinetic disposition of Taxol in children was studied, and preliminary evidence of the activity of Taxol against pediatric solid tumors was assessed.

PATIENTS AND METHODS

Twenty-four-hour continuous infusions of Taxol were administered every 21 days to children (median age, 12 years; range, 2 to 22) with refractory solid tumors. Doses ranged from 200 to 420 mg/m2, there was no intrapatient dose escalation.

RESULTS

A total of 62 courses of Taxol were administered to 31 patients. Two patients developed acute anaphylaxis during their second infusion of taxol at doses of 200 mg/m2 and 350 mg/m2, respectively. No other allergic reactions were documented. Myelosuppression occurred at all dose levels, but was of short duration (< or = 7 days) and did not appear to increase with consecutive courses or at higher dosage levels. A stocking-and-glove peripheral neuropathy became evident at doses > or = 290 mg/m2. Dose-limiting neurotoxicity occurred at 420 mg/m2 and comprised a significant fine-motor and peripheral neuropathy in one patient, and a tonic-clonic seizure in another. End-of-infusion plasma concentrations ranged from 0.40 to 6.4 mumol/L, and were not found to be dose-dependent over the range of doses studied. A complete response was documented in one patient, partial response in two, and minimal response in one for an overall response rate of 13%.

CONCLUSION

Neurotoxicity was dose-limiting when Taxol was administered by 24-hour continuous infusion to pediatric patients with relapsed solid tumors. In this population, the recommended dose for phase II trials is 350 mg/m2/d.
Impact of megatherapy on survival after relapse from stage 4 neuroblastoma in patients over 1 year of age at diagnosis: a report from the European Group for Bone Marrow Transplantation.
Authors: Ladenstein R , Lasset C , Hartmann O , Frappaz D , Garaventa A , Klingebiel T , Zucker J M , Coze C , Burdach S , Gadner H
Published: February 2017

PURPOSE

Relapse from stage 4 neuroblastoma usually carries a poor prognosis. A retrospective study using the European Bone Marrow Transplant (EBMT) Solid Tumor Registry was undertaken to define the role of megatherapy (MGT) in relapsed patients.

PATIENTS AND METHODS

After relapse, 33 boys and 15 girls with previous stage 4 neuroblastoma received intensification by MGT followed by either autologous (n = 42) or allogeneic (n = 6) bone marrow rescue in 11 European institutions. The median age at diagnosis was 47 months (range, 14 to 134) and the median interval from diagnosis to relapse was 16 months (range, 4 to 94). Thirty patients had received only conventional-dose primary treatments (group A), whereas 18 patients had previously received intensification with MGT (group B). The median follow-up time of the total group is 95 months (range, 25 to 185).

RESULTS

The actuarial overall survival rate at 2 years after MGT for relapse is 27% for group A and 0% for group B (P = .02). Three adverse, independent prognostic factors were confirmed by multivariate analysis using the Cox proportional hazards regression model: an interval of less than 12 months between diagnosis and relapse (P < .0001), nonresponding or untreated relapse (P = .0002), and previous MGT during primary treatments (P = .055). None of the other variables analyzed, such as sex, age, bone or bone marrow involvement at diagnosis or at relapse, and type of MGT at relapse, influenced outcome in this patient cohort.

CONCLUSION

Responding patients who relapse more than 12 months from diagnosis who had not received previous MGT appear to benefit from consolidation MGT. Relapse patients who do not fulfill these criteria gain no advantage from this cost-intensive procedure and should be treated differently.
Therapy-related acute myeloid leukemia with t(8;21), inv(16), and t(8;16): a report on 25 cases and review of the literature.
Authors: Quesnel B , Kantarjian H , Bjergaard J P , Brault P , Estey E , Lai J L , Tilly H , Stoppa A M , Archimbaud E , Harousseau J L
Published: February 2017

PURPOSE

To analyze therapy-related acute myeloid leukemias (tAMLs) with t(8;21), inv(16), or t(8;16).

PATIENTS AND METHODS

Twenty-five patients with tAML and t(8;21)(q22;q22), inv(16)(p13;q22), or t(8;16)(p11;p13) from seven centers, along with 23 previously published cases, were studied.

RESULTS

Twenty-six, 16, and six patients, respectively, had t(8;21), inv(16), and t(8;16). Prior cancer was a solid tumor in 27 cases, and a hematologic malignancy in all other patients. Five patients had received prior radiotherapy (RT) alone, and 43 had received prior chemotherapy with or without RT. Prior chemotherapy included a drug that directly reacts with DNA (alkylating agent or cisplatin) and/or an agent that targets topoisomerase II (ATTop, an anthracycline or derivative or, less often, epipodophyllotoxin) in most patients. The interval between prior tumor and diagnosis of tAML was less than 3 years in most cases, and only seven patients had a preleukemic phase of disease. Morphology was M2 AML for t(8;21), M4eo for inv(16), and M4 or M5 for t(8;16). Sixteen of 21 (76%), 12 of 14 (86%), and zero of four patients with t(8;21), inv(16), and t(8;16), respectively, achieved complete remission (CR) with intensive chemotherapy. The actuarial disease-free survival rate at 24 months was 47% and 54% in patients with t(8;21) and inv(16), respectively.

CONCLUSION

Like other tAMLs with a karyotype specific of de novo AML [balanced 11q23 rearrangement or t(15;17)], tAMLs with t(8;21), inv(16), or t(8;16) are usually characterized by a short latent period, previous treatment often combining a drug that directly reacts with DNA and an ATTop, and absence of preleukemic phase. Hematologic characteristics and response to treatment are also identical to those of de novo AML with the same karyotypes.
Inadequacy of ultrasonography for monitoring response to treatment of liver metastases.
Authors: Giovagnoni A , Piga A , Argalia G , Giuseppetti G M , Ercolani P , Cellerino R
Published: February 2017

PURPOSE

We prospectively evaluated the clinical efficacy of ultrasonography (US) in monitoring the effect of medical treatment in patients with liver metastases, by comparing serial US assessment with serial magnetic resonance imaging (MRI) evaluation and clinical outcome in a group of 41 patients with solid tumors.

PATIENTS AND METHODS

Both examinations were performed in patients with metastatic liver disease at the start of a new treatment modality and monthly thereafter for 3 months; close monitoring was prolonged beyond the third month in cases in which there was disagreement between the two techniques and the clinical course was not conclusive.

RESULTS

Planned follow-up was completed in 37 cases. There was limited concordance between the two examinations: in 21 cases only (56.8%), US and MRI gave concordant information on the evolution of hepatic metastases; in eight cases, both agreed on progression of disease (PD), in 11 cases on stable disease (SD), and in one case each on partial response (PR) and complete response (CR). In the remaining 16 cases (43.2%), there was disagreement between the two examinations. On the basis of subsequent clinical course, this discrepancy was shown to be due to US inadequacy in 13 cases and to MRI inadequacy in one case; in two cases, the clinical course was not conclusive. The most striking limits of US appeared to be twofold: (1) a progressive appearance, with chemotherapy, of a diffusely inhomogeneous structure of the liver, resulting in obscuration of focal lesions (and a subsequent judgement of CR) in cases in which lesions were, on the contrary, detected at MRI and usually confirmed by subsequent clinical course; and (2) false US-determined PD in cases in which lesions proven at baseline MRI were noted at US only after one to two courses of therapy.

CONCLUSION

We conclude that US, which is known to be inaccurate for screening of liver metastases, is unreliable for the follow-up of metastatic liver disease; despite its wide availability, low cost, and noninvasiveness, critical therapeutic decisions should not be made based on the outcome of this test.
Central lymphatic irradiation for stage III nodular malignant lymphoma: long-term results.
Authors: Jacobs J P , Murray K J , Schultz C J , Wilson J F , Goswitz M S , Stevens C W , Cox J D
Published: February 2017

PURPOSE

To report the long-term results of central lymphatic irradiation for stage III nodular malignant lymphoma.

PATIENTS AND METHODS

Between 1969 and 1985, 34 patients (26 with nodular poorly differentiated lymphoma, four with nodular mixed lymphocytic/histiocytic lymphoma, and four with nodular histiocytic lymphoma) were treated with central lymphatic irradiation. Median age of the group was 51 years (range, 30 to 73). There were 15 men and 19 women. Staging work-up included a physical examination and bone marrow biopsy in all patients. Seventy-four percent had a lymphangiogram (LAG) and 44% a laparotomy (LAP). Eighty-two percent had either a LAP or a LAG. Thirty-two patients were Ann Arbor stage IIIA and two were stage IIIB. All patients received lymphatic irradiation that encompassed cervical, supraclavicular, axillary, mediastinal, paraaortic, mesenteric, pelvic, and femoral lymphatics to total doses ranging from 20 to 30 Gy in 1.0- to 1.8-Gy fractions. Waldeyer's ring was initially treated in 17 patients. Follow-up information is available on all 34 patients. Median follow-up is 9 years, 8 months (range, 15 to 244 months).

RESULTS

Life-table actuarial overall, disease-free, and cause-specific survival rates at 15 years are 28%, 40%, and 46%, respectively. Only one relapse was observed after 9 years. Disease-free survival was significantly improved in patients with five or fewer sites of involvement (P = .02). Age, sex, B symptoms, histology, and technique of irradiation were not prognostically significant. Salvage therapy, including further irradiation and/or chemotherapy, was delivered to 20 patients. Ten percent of these patients remain alive without evidence of disease. Toxicity data were available for the patients treated at the Medical College of Wisconsin (MCW). Radiation Therapy Oncology Group (RTOG) acute hematologic, gastrointestinal, and salivary toxicity scores were < or = 2 in 83% of patients. Late toxicity scores were < or = 2 in 96%. Persistent xerostomia was noted in 23% of patients who received initial treatment to Waldeyer's ring.

CONCLUSION

These results suggest that initial comprehensive central lymphatic irradiation may be the preferred approach to achieve a durable relapse-free interval for this group of patients.
Long-term reduction in sperm count after chemotherapy with and without radiation therapy for non-Hodgkin's lymphomas.
Authors: Pryzant R M , Meistrich M L , Wilson G , Brown B , McLaughlin P
Published: February 2017

PURPOSE

Treatment of lymphomas with combination chemotherapy with or without radiation therapy (XRT) can result in long-term or permanent azoospermia.

PATIENTS AND METHODS

Semen analyses of lymphoma patients were performed before, during, and after treatment with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-Bleo) chemotherapy. Some of the patients also received other drugs or radiation therapy.

RESULTS

Although no patients were azoospermic before treatment, all were rendered azoospermic during treatment. Following the completion of treatment, the fraction of patients whose sperm counts recovered increased gradually over 5 years and plateaued by 7 years, with two thirds of the men achieving normospermic levels. Scattered gonadal radiation dose and cumulative cyclophosphamide dose were found to be independently significant determinants of recovery: the fraction of patients whose sperm counts recovered to 10 x 10(6)/mL were 83%, 47%, and 20% for those who received less than 9.5 g/m2 of cyclophosphamide, greater than 9.5 g/m2 of cyclophosphamide, and pelvic XRT, respectively. The inclusion of additional drugs and interferon alfa did not significantly affect the long-term recovery of spermatogenesis.

CONCLUSION

Pelvic XRT and cumulative cyclophosphamide dosages greater than 9.5 g/m2 are associated with a high risk of permanent sterility in lymphoma patients treated with the CHOP-Bleo regimen.
Goals of palliative cancer therapy.
Authors: Porzsolt F , Tannock I
Published: February 2017

The major conclusions of the Workshop on Goals of Palliative Cancer Therapy are as follows: 1. The goals of any cancer therapy should be stated explicitly. 2. If the goal of treatment is palliation, this should be documented according to one of the established and validated methods for assessment of quality of life. Several validated methods are available, and although imperfect, have been shown to give reliable information. 3. The use of simple measures of quality of life (eg, symptom checklists, pain assessment cards) should become routine in oncology practice. The act of introducing such measures improves palliation. 4. Measures of cost-effectiveness should be used more widely in clinical decision making to ensure the appropriate deployment of resources. 5. There must be improved education of all health professionals with regard to the multiple methods for provision of palliative treatment to cancer patients and the assessment of palliation.
Effect of relative cumulative dose-intensity on survival of patients with urothelial cancer treated with M-VAC.
Authors: Scher H I , Geller N L , Curley T , Tao Y
Published: February 2017

PURPOSE

To evaluate the received dose-intensity in a mature data set of patients with advanced urothelial cancer who received at least one cycle of the methotrexate (M), vinblastine (V), Adriamycin ([A], doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin (C) regimen (M-VAC).

PATIENTS AND METHODS

Received dose-intensity was evaluated over time by summing doses over cycles for each patient, cumulating treatment times, and assuming four cycles of chemotherapy were planned. Relative cumulative dose-intensity was then calculated for individual patients at the end of each cycle. To assess a relationship with survival, relative cumulative dose-intensity was then used as a time-dependent covariate in Cox regression.

RESULTS

The median follow-up was 6 years and median survival 13.3 months, with 20 patients alive at the time of analysis. Out of a maximum of 1.0, the median relative dose-intensity for the M-VAC combination decreased from .69 to .59 from cycle 1 to cycle 4. Similarly, a decrease from .68 to .62 and from .80 to .72 was observed for A and C, respectively. The median received dose-intensity for A was 6.0 mg/m2/wk, and for C 14 mg/m2/wk. Neither the four-cycle relative cumulative dose-intensity for the M-VAC combination, nor the relative cumulative dose-intensities for A or C were found to be significant prognostic factors.

CONCLUSION

The absence of an effect for received dose-intensity on survival may reflect the low dose-intensities of the components of the regimen actually delivered in this study. The results question whether the individual agents can be escalated sufficiently, with growth factor support, to improve significantly complete response proportions, a prerequisite for increasing the proportion of long-term survivors.
Second cancer risk following testicular cancer: a follow-up study of 1,909 patients.
Authors: van Leeuwen F E , Stiggelbout A M , van den Belt-Dusebout A W , Noyon R , Eliel M R , van Kerkhoff E H , Delemarre J F , Somers R
Published: February 2017

PURPOSE

Improved survival in testicular cancer has been accompanied by concern about long-term side effects of therapy. We assessed the evolution of second cancer (SC) risk over a prolonged follow-up period, which has been rarely studied in large patient series.

PATIENTS AND METHODS

We estimated the risk of SCs in 1,909 patients with testicular cancer diagnosed in the Netherlands from 1971 to 1985. Complete medical information was obtained up to at least January 1988 for 92% of patients. Median follow-up was 7.7 years. For 89% of second tumors the diagnosis was confirmed through review of histologic slides; for an additional 8%, the diagnosis was verified by pathology reports only.

RESULTS

Seventy-eight patients developed a SC 1 year or more after start of treatment, as compared with 47.6 expected on the basis of incidence rates in the general population (relative risk [RR], 1.6; 95% confidence interval [CI], 1.3 to 2.1). The mean 15-year actuarial risk of all SCs was 9.8% (95% CI, 7.5% to 12.8%). Significantly increased RRs were observed for all gastrointestinal cancers combined (RR, 2.6; 95% CI, 1.7 to 3.9), stomach cancer (RR, 3.7; 95% CI, 1.8 to 6.8), contralateral testicular cancer (CLTC) (RR, 35.7; 95% CI, 21.8 to 55.2), and leukemia (RR, 5.1; 95% CI, 1.4 to 13.0). Patients who had received irradiation to the paraaortic lymph nodes and who survived testicular cancer for more than 5 years were at particularly high risk of developing stomach cancer (RR, 6.9; 95% CI, 3.3 to 12.7). The median interval between the diagnosis of testicular cancer and stomach cancer was 12.4 years. Patients treated with chemotherapy (CT) did not experience an increase in SCs in general. Indeed, CT-treated patients, as compared with those who received radiotherapy (RT), or surgery alone, had significantly reduced risk of CLTC. This finding might be attributed to an eradicating effect of CT on carcinoma in situ or subclinical CLTC. The excess risk of leukemia was not found to be clearly related to CT.

CONCLUSION

Testicular cancer patients who receive RT experience elevated risk of gastrointestinal tumors. CT does not seem to increase SC risk and may even decrease the risk of a CLTC. Following testicular cancer, the 15-year actuarial risk of all SCs is only about half the risk experienced by patients with Hodgkin's disease.
Osteogenic sarcoma with clinically detectable metastasis at initial presentation.
Authors: Meyers P A , Heller G , Healey J H , Huvos A , Applewhite A , Sun M , LaQuaglia M
Published: February 2017

PURPOSE

Chemotherapy and surgery have improved the length of survival for patients with osteogenic sarcoma (OS) who present without metastatic disease. We reviewed our experience with patients with OS who presented with clinically detectable metastasis to determine the prognostic factors and the effects of surgery on the primary tumor and on metastatic disease.

PATIENTS AND METHODS

From 1975 to 1984 we treated 62 patients who had previously untreated OS with metastasis detected at presentation. All of these patients received intensive chemotherapy that included high-dose methotrexate; doxorubicin; and bleomycin, cyclophosphamide, and dactinomycin (BCD). Selected patients also received cisplatin. The intent of surgery was resection of the primary tumor and metastatic disease.

RESULTS

Survival was extremely poor; only 11% of patients survived, with a median survival of 20 months. Survival was not affected by use of preoperative chemotherapy versus immediate surgery, and did not correlate with serum lactate dehydrogenase (LDH) level, alkaline phosphatase level, or the site of the primary tumor. Survival did correlate with age, location of metastatic disease, histologic response to preoperative chemotherapy, and completeness of surgical resection of all sites of tumor. Resection of all sites of tumor identified at initial presentation was necessary for survival.

CONCLUSION

OS that presents with metastatic disease has a very poor prognosis with therapy, although therapy has achieved good results for patients without metastasis detected at diagnosis. Aggressive surgical resection of tumor is necessary for survival. The use of novel therapies at initial presentation is justified with this group of patients.
Donor leukocyte infusions for chronic myeloid leukemia relapsed after allogeneic bone marrow transplantation.
Authors: Bär B M , Schattenberg A , Mensink E J , Geurts Van Kessel A , Smetsers T F , Knops G H , Linders E H , De Witte T
Published: February 2017

PURPOSE

Treatment options for patients with chronic myeloid leukemia (CML) who relapse after allogeneic bone marrow transplantation (BMT) are limited. Treatment with lymphocytes from the original marrow donor and the influence on the malignant clone was studied in these patients.

PATIENTS AND METHODS

Seven patients with CML that had relapsed after BMT with T-cell-depleted grafts were treated. Six patients received leukocyte infusions from the original marrow donor. One patient received a second BMT with unseparated marrow from the same sibling donor. Chimerism was studied using erythrocyte and cytogenetic markers. Residual leukemic cells were monitored by cytogenetic analysis of the Philadelphia (Ph) chromosome and by polymerase chain reaction (PCR) of the breakpoint cluster region/Abelson (BCR-ABL) fusion gene.

RESULTS

In five patients with hematologic relapse, the Ph chromosome disappeared 1 to 3 months after the leukocyte infusions. Cytogenetic analysis and in situ hybridization (ISH) showed only donor cells during further follow-up. Four to five patients became negative for the BCR-ABL translocation by PCR. Graft-versus-host disease (GVHD) always preceded response and was severe in two patients. One patient with cytogenetic relapse showed no response after leukocyte infusions. GVHD after second BMT was of moderate severity. One year after second BMT, PCR for the BCR-ABL translocation was negative.

CONCLUSION

Infusion of donor leukocytes is an effective treatment with a low mortality in patients with CML relapsed after BMT with a T-cell-depleted graft. Longer follow-up and more patients will be needed to know whether cure will be permanent.
The Functional Assessment of Cancer Therapy scale: development and validation of the general measure.
Authors: Cella D F , Tulsky D S , Gray G , Sarafian B , Linn E , Bonomi A , Silberman M , Yellen S B , Winicour P , Brannon J
Published: February 2017

PURPOSE

We developed and validated a brief, yet sensitive, 33-item general cancer quality-of-life (QL) measure for evaluating patients receiving cancer treatment, called the Functional Assessment of Cancer Therapy (FACT) scale.

METHODS AND RESULTS

The five-phase validation process involved 854 patients with cancer and 15 oncology specialists. The initial pool of 370 overlapping items for breast, lung, and colorectal cancer was generated by open-ended interview with patients experienced with the symptoms of cancer and oncology professionals. Using preselected criteria, items were reduced to a 38-item general version. Factor and scaling analyses of these 38 items on 545 patients with mixed cancer diagnoses resulted in the 28-item FACT-general (FACT-G, version 2). In addition to a total score, this version produces subscale scores for physical, functional, social, and emotional well-being, as well as satisfaction with the treatment relationship. Coefficients of reliability and validity were uniformly high. The scale's ability to discriminate patients on the basis of stage of disease, performance status rating (PSR), and hospitalization status supports its sensitivity. It has also demonstrated sensitivity to change over time. Finally, the validity of measuring separate areas, or dimensions, of QL was supported by the differential responsiveness of subscales when applied to groups known to differ along the dimensions of physical, functional, social, and emotional well-being.

CONCLUSION

The FACT-G meets or exceeds all requirements for use in oncology clinical trials, including ease of administration, brevity, reliability, validity, and responsiveness to clinical change. Selecting it for a clinical trial adds the capability to assess the relative weight of various aspects of QL from the patient's perspective.
Survival comparison of radiosurgery-eligible and -ineligible malignant glioma patients treated with hyperfractionated radiation therapy and carmustine: a report of Radiation Therapy Oncology Group 83-02.
Authors: Curran W J , Scott C B , Weinstein A S , Martin L A , Nelson J S , Phillips T L , Murray K , Fischbach A J , Yakar D , Schwade J G
Published: February 2017

PURPOSE

The purpose is twofold: (1) to identify the malignant glioma patients treated in a trial of hyperfractionated radiotherapy (RT) and carmustine (BCNU) who may have been eligible for a stereotactic radiosurgery (SRS) boost; and (2) to compare survival of such patients with that of those considered SRS-ineligible.

PATIENTS AND METHODS

From January 1983 to July 1989, 778 malignant glioma patients were enrolled on Radiation Therapy Oncology Group (RTOG) 83-02, a randomized phase I/II hyperfractionated RT dose-escalation trial with BCNU chemotherapy. The SRS criteria used in a single-institution trial were applied to these patients; they are: Karnofsky performance status (KPS) of greater than 60; well-circumscribed tumor less than 4.0 cm; no subependymal spread; and a location not adjacent to brainstem or optic chiasm.

RESULTS

Eighty-nine patients (11.9%) were identified as potentially SRS-eligible. The median survival times (MST) and 18-month survival rates of the 89 eligible and 643 ineligible patients were 14.4 versus 11.7 months and 40% versus 27%, respectively (P = .047). The MST and 18-month survival rate of the 544 SRS-ineligible patients with KPS greater than 60 were 12.1 months and 29%, respectively, and were not statistically inferior to the survival of the SRS-eligible group (P = .21). Multivariate analysis revealed age, KPS, and histopathology to be strongly predictive of survival, and SRS eligibility was also significantly predictive (P = .047).

CONCLUSION

SRS-eligible patients enrolled on RTOG 83-02 had survival superior to that of the SRS-ineligible group, and this advantage is mainly due to the selection of a subgroup with a high minimum KPS.
Interleukin-2-induced thyroid dysfunction is correlated with treatment duration but not with tumor response.
Authors: Kruit W H , Bolhuis R L , Goey S H , Jansen R L , Eggermont A M , Batchelor D , Schmitz P I , Stoter G
Published: February 2017

PURPOSE

To analyze the putative relationship between immunotherapy-associated dysthyroidism and the probability of a tumor response.

PATIENTS AND METHODS

A total of 89 consecutive patients with advanced cancer were treated with interleukin-2 (IL2)-based immunotherapy in a prospective study.

RESULTS

Twenty patients developed thyroid dysfunction. Repeatedly positive tests for thyroid antibodies developed in 28% of the patients. Twenty-two patients achieved a response. There was no relationship between the formation of antibodies and the probability of response. There appeared to be a trend toward a relationship between thyroid dysfunction and response (P = .23). A strong relationship was found between response on the one hand and cumulative dose of IL2 (P = .01) and treatment duration with IL2 (P = .025) on the other. The frequency of thyroid dysfunction was also significantly correlated with treatment duration (P = .001). After adjustment for cumulative dose of IL2 and treatment duration, no relationship between thyroid dysfunction and response remained (P = .99).

CONCLUSION

There is no relationship between thyroid dysfunction and the probability of tumor response. Thyroid dysfunction is merely a function of treatment duration and cumulative dose of IL2.
Prognostic role of serum beta 2-microglobulin in Hodgkin's disease.
Authors: Dimopoulos M A , Cabanillas F , Lee J J , Swan F , Fuller L , Allen P K , Hagemeister F B
Published: February 2017

PURPOSE

To evaluate the role of serum beta 2-microglobulin (beta 2M) in the prognosis of patients with Hodgkin's disease.

PATIENTS AND METHODS

One hundred sixty previously untreated patients with Hodgkin's disease had serum beta 2M levels determined before initiation of treatment. Serum beta 2M was tested for its correlation with known prognostic factors for patients with Hodgkin's disease. These variables, including beta 2M, were correlated with complete remission (CR) rate and time to treatment failure (TTF). Univariate and multivariate analyses were performed.

RESULTS

Serum beta 2M levels greater than 2.5 mg/L were found in 29% of patients. Such elevation was more common in patients with more advanced-stage disease. Elevated serum beta 2M was an independent and powerful factor in the prediction of lower response rate and shorter TTF. Its impact appeared to be more significant in patients with advanced disease.

CONCLUSION

Serum beta 2M appears to correlate with tumor stage in patients with Hodgkin's disease and elevated serum levels of this polypeptide predict a less favorable prognosis.
Node status has prognostic significance in the multimodality therapy of diffuse, malignant mesothelioma.
Authors: Sugarbaker D J , Strauss G M , Lynch T J , Richards W , Mentzer S J , Lee T H , Corson J M , Antman K H
Published: February 2017

PURPOSE

We studied a multimodality approach using extrapleural pneumonectomy, chemotherapy, and radiotherapy in patients with malignant pleural mesothelioma.

PATIENTS AND METHODS

From 1980 to 1992, 52 selected patients, underwent treatment. Median age was 53 years (range, 33 to 69). Initial patient evaluation was performed by a multimodality team. Pathologic diagnosis was reviewed and confirmed before therapy. Patients with no medical contraindication and potentially resectable mesothelioma on computed tomography (CT) (magnetic resonance imaging [MRI] when it became available) received extrapleural pneumonectomy, cyclophosphamide, doxorubicin, and cisplatin (CAP) chemotherapy, and radiotherapy.

RESULTS

Perioperative morbidity and mortality rates were 17% and 5.8%, respectively. The overall median survival duration is 16 months (range, 1 month to 8 years). The 32 patients with epithelial histologic variant had 1-, 2-, and 3-year survival rates of 77%, 50%, and 42%, respectively. Patients with mixed and sarcomatous cell disease had 1- and 2-year survival rates of 45% and 7.5%; no patient lived longer than 25 months (P < .01). At resection, positive regional mediastinal lymph nodes were found in 13. Positive lymph nodes were associated with poorer survival than were negative nodes (P < .01). Patients with epithelial variant and negative mediastinal lymph nodes had a survival rate of 45% at 5 years.

CONCLUSION

Multimodality therapy including extrapleural pneumonectomy has acceptable morbidity and mortality for selected patients. Prolonged survival occurred in patients with epithelial histologic variant and negative mediastinal lymph nodes. These data provide a rationale for a revised staging system for malignant pleural mesothelioma; furthermore, they permit stratification of patients into groups likely to benefit from aggressive multimodality treatment.
Adherence to oral tamoxifen: a comparison of patient self-report, pill counts, and microelectronic monitoring.
Authors: Waterhouse D M , Calzone K A , Mele C , Brenner D E
Published: February 2017

PURPOSE

Recent innovations allow the integration of microelectronics into drug packaging, providing a continuous record of the interactions of the patient with the drug package. We hypothesized that adherence to oral tamoxifen, as measured by a pressure-activated microelectronic monitoring device, would be significantly discrepant from traditional measures of patient adherence, ie, patient self-report (SR) and pill counts (PCs).

PATIENTS AND METHODS

Twenty-six patients receiving oral tamoxifen therapy were assessed by patient SR, PCs, and Medication Event Monitoring System (MEMS; Aprex Corp, Fremont, CA) microelectronic monitoring. A microprocessor in the MEMS cap recorded each opening as a presumptive dose, listing the date, time, and duration of opening for later retrieval on a microcomputer. Patients were not informed that their adherence was to be monitored electronically or that PCs would be performed.

RESULTS

A total of 2,102 days (70.1 months) of tamoxifen therapy were monitored; patients were monitored for a mean of 2.92 months of tamoxifen therapy. SR adherence to oral tamoxifen was significantly higher than that suggested by either PCs (SR missed doses only v PC, P = .008) or MEMS adherence monitoring (SR missed doses only v MEMS missed doses only, P = .005; SR dosing-interval errors only v MEMS dosing-interval errors only, P < .0001; SR all dosing errors v MEMS all dosing errors, P < .0005). PC data also suggested significantly higher adherence rates than MEMS monitoring.

CONCLUSION

Microelectronic adherence monitoring provides both confirmatory and complimentary data regarding adherence behavior, while also allowing for the evaluation of patterns of nonadherence. Patient SRs and PCs likely overestimate the degree to which patients adhere to their tamoxifen regimen.
Detection of occult lymphoma in the peripheral blood and bone marrow of patients with untreated early-stage and advanced-stage follicular lymphoma.
Authors: Berinstein N L , Reis M D , Ngan B Y , Sawka C A , Jamal H H , Kuzniar B
Published: February 2017

PURPOSE

The object of this study was to compare the relative sensitivities of morphologic, immunophenotypic, gene rearrangement, cytogenetic, and polymerase chain reaction (PCR) analyses in the detection of lymphoma cells in the bone marrow and peripheral blood of patients with follicular lymphoma.

PATIENTS AND METHODS

Bone marrow and peripheral-blood samples from 28 newly diagnosed patients with follicular lymphoma referred from several different medical centers were assessed. Routine morphologic assessment was performed initially and the remainder of the sample was aliquoted for DNA extraction to be used for gene rearrangement and PCR analyses and for immunophenotypic and cytogenetic analyses where a sufficient amount of sample remained.

RESULTS

Morphologic assessment of the bone marrow was positive for lymphoma cells in 11 of 28 patients. PCR amplification of t(14;18) breakpoint DNA detected lymphoma cells in 17 of 24 patients assessed. Morphologic assessment detected lymphoma cells in three bone marrow samples that were negative by PCR. PCR analysis was the only method able to detect circulating lymphoma cells in peripheral blood at diagnosis and was positive in 15 of 24 samples. The other methods of assessment did not show lymphoma in any samples in which lymphoma was not detected by morphologic or PCR analysis. Lymphoma cells were found in the bone marrow and/or peripheral blood as frequently in early-stage patients as in advanced-stage patients.

CONCLUSION

PCR amplification of t(14;18) breakpoint DNA together with morphologic assessment had the highest yield of detecting lymphoma cells in the bone marrow and/or peripheral blood of our population of newly diagnosed patients with follicular lymphoma. The clinical significance and prognostic importance of lymphoma cells detected by PCR in the bone marrow and/or peripheral blood of newly diagnosed follicular lymphoma patients awaits long-term follow-up data of these and additional patients.
Why women gain weight with adjuvant chemotherapy for breast cancer.
Authors: Demark-Wahnefried W , Winer E P , Rimer B K
Published: February 2017

PURPOSE

Among breast cancer patients receiving adjuvant chemotherapy, weight gain is a common side effect that may decrease quality of life and potentially threaten survival. Weight gain during treatment is a problem that is clinically well appreciated, and one that has been studied by a number of investigators.

DESIGN

A literature review was conducted to address each of the following issues: (1) the prevalence and magnitude of weight gain in women receiving adjuvant chemotherapy for early-stage breast cancer, (2) factors that might affect the amount of weight gained, (3) adverse consequences of weight gain, (4) mechanisms potentially responsible for weight gain, and (5) current dietary intervention programs directed toward women receiving adjuvant chemotherapy.

RESULTS

Weight gain is associated with a number of adverse effects in breast cancer patients receiving adjuvant chemotherapy. Weight gains are exaggerated in premenopausal women and women receiving multiagent regimens. Little research has been conducted to investigate the underlying mechanisms that contribute to weight gain in this population.

CONCLUSION

Interventions to prevent weight gain during adjuvant chemotherapy are underway; however, little research has been conducted to investigate the underlying mechanisms of energy imbalance. Although changes in resting metabolic rate, thermogenesis, physical activity, and dietary intake are all plausible, no firm data exist to support any of these mechanisms. There is a need for research that explores the relative contribution of each of these factors to energy imbalance, so that optimally effective interventions can be created and implemented to combat this problem.
Myeloablative radiochemotherapy and hematopoietic stem-cell rescue in poor-prognosis Ewing's sarcoma.
Authors: Burdach S , Jürgens H , Peters C , Nürnberger W , Mauz-Körholz C , Körholz D , Paulussen M , Pape H , Dilloo D , Koscielniak E
Published: February 2017

PURPOSE

The prognosis of patients with multifocal primary and early or multiple relapsed Ewing's sarcoma is poor with conventional chemoradiotherapy and surgery. We evaluated the efficacy and feasibility of a myeloablative regimen administered as consolidation treatment for these patients.

PATIENTS AND METHODS

The ablative regimens consisted of simultaneous radiochemotherapy: 12 Gy hyperfractionated total-body irradiation (TBI; two doses of 1.5 Gy for 4 days) plus fractionated high-dose melphalan (30 to 45 mg/m2 for 4 days) followed by high-dose etoposide (40 to 60 mg/kg) with or without carboplatin (900 to 1,500 mg/m2) (hyper-ME +/- C). These regimens were applied in a dose-escalation study that included 17 patients. All patients underwent remission induction chemotherapy and local treatment before myeloablative therapy. Seven patients had multifocal primary Ewing's sarcoma, and 10 had early or multiple relapse. We performed a matched-cohort analysis of the 17 grafted patients with 41 historic controls matched for sex, age, diagnosis, extent of disease, interval from diagnosis to transplant in the transplant group, and interval from diagnosis to relapse in the control group.

RESULTS

The probability of relapse in the study patients is 52% at 6 years after the last event before transplantation. In the control group, the probability of relapse at 6 years was 98%. Eight of 17 treated patients are alive in complete remission at a median observation time of 49 months (range, 19 to 76) from the last event before transplantation. Probability of relapse-free survival in the study patients is 45% +/- 12% at 6 years after the last event before transplant, compared with 2% +/- 2% for the historic control group.

CONCLUSION

Myeloblative therapy with hyper-ME +/- C radiochemotherapy can improve the prognosis of multifocal primary and early or multiple relapsing Ewing's sarcoma.
Impact of axillary lymph node dissection on the therapy of breast cancer patients.
Authors: Lin P P , Allison D C , Wainstock J , Miller K D , Dooley W C , Friedman N , Baker R R
Published: February 2017

PURPOSE

We studied a series of 283 breast cancer patients retrospectively to determine the actual benefits of axillary lymph node dissection (ALND) for these patients.

PATIENTS AND METHODS

The records of 283 women with invasive breast cancer treated between 1988 and 1990 were reviewed for histologic status of the axillary lymph nodes, tumor size, DNA content, hormone-receptor values, and actual adjuvant treatments received.

RESULTS

ALND was of possible therapeutic benefit for the 15% (43 of 283) of patients who had clinically positive nodes. Nodal metastases were found in 86% (37 of 43) of patients in this subgroup. ALND alone determined the indication for standard adjuvant therapy for a group of 31% (88 of 283) of patients who had favorable primary biopsy findings and clinically negative axillary nodes; ALND proved that 13% (11 of 88) of these latter patients had positive nodes. For 54% (152 of 283) of patients who had clinically negative nodes and unfavorable biopsies, ALND played no role in the decision as to whether standard adjuvant therapy was indicated. Only 5% (seven of 152) and 3% (four of 152) of these latter patients received radiation therapy and/or high-dose adjuvant chemotherapy, respectively, because of ALND.

CONCLUSION

The benefits of ALND vary greatly for different groups of breast cancer patients, and controlled studies may be needed to determine whether ALND is necessary for all breast cancer patients.
Contralateral breast cancer: clinical characteristics and impact on prognosis.
Authors: Healey E A , Cook E F , Orav E J , Schnitt S J , Connolly J L , Harris J R
Published: February 2017

PURPOSE

To determine the characteristics of patients with unilateral breast cancer who subsequently develop contralateral breast cancer (CBC), to assess their prognosis relative to patients who do not develop a CBC, and to assess the feasibility of using conservative surgery (CS) and radiotherapy (RT) to treat CBC.

MATERIALS AND METHODS

Of 1,624 women treated with CS and RT for unilateral stage I or II breast cancer at the Joint Center for Radiation Therapy, 77 developed an invasive CBC. Sixty-two CBCs were treated with CS and RT. The median follow-up duration was 95 months from the time of initial breast cancer diagnosis, and 63 months from CBC diagnosis.

RESULTS

The cumulative actuarial rate of CBC was 7.0% at 10 years, and the annual incidence rate for CBC was relatively constant. Young age predicted for CBC. When age was analyzed by decade the relative risk (RR) for older patients compared with younger patients was 0.79 (95% confidence interval [CI], 0.62 to 1.01). The presence of lobular carcinoma in situ (LCIS), higher tumor stage, and lack of adjuvant systemic therapy also predicted for CBC with borderline significance. Multivariate analyses showed that CBC was associated with a statistically significant greater likelihood of local recurrence (LR) or distant recurrence (RR, 1.68; 95% CI, 1.03 to 2.71), and distant-only recurrence (RR, 2.17; 95% CI, 1.28 to 3.69). Among assessable patients treated with bilateral RT, 28 of 31 ipsilateral and 11 of 11 contralateral breasts had an excellent or good overall cosmetic outcome at 5 years, and treatment-related complications were minimal.

CONCLUSION

We conclude that (1) young age is associated with a greater likelihood of CBC, (2) patients who develop a CBC have a greater subsequent risk of distant relapse as compared with patients without CBC, and (3) it is feasible to deliver sequential nonoverlapping bilateral RT without compromising the cosmetic outcome or increasing complications.
Prognostic significance of histopathologic response to chemotherapy in nonmetastatic Ewing's sarcoma of the extremities.
Authors: Picci P , Rougraff B T , Bacci G , Neff J R , Sangiorgi L , Cazzola A , Baldini N , Ferrari S , Mercuri M , Ruggieri P
Published: February 2017

PURPOSE

To evaluate more accurately the effectiveness of preoperative chemotherapy in the treatment of patients with Ewing's sarcoma, we studied histopathologically the chemotherapeutic response and correlated it to oncologic outcome.

PATIENTS AND METHODS

Between June 1983 and December 1989, 68 patients with nonmetastatic Ewing's sarcoma of the extremities were treated at our institute with preoperative chemotherapy (without radiation therapy) and surgery. The specimens were retrospectively evaluated for areas of viable tumor cells and graded from I to III (macroscopic, microscopic, or no residual disease, respectively) in a blinded fashion. Clinical follow-up data were available on all patients for a mean of 60 months (range, 32 to 111).

RESULTS

This histopathologic analysis was strongly correlated with oncologic outcome (P = .004). Patients who demonstrated grade III response (no identifiable viable tumor nodules present) had improved 5-year disease-free survival rates as compared with patients with grade II (microscopic nodes present; P = .023; 90% v 53%) and grade I responses (macroscopic nodules present; P = .0003; 90% v 32%). Patients with grade II necrosis had statistically improved survival rates over those with grade I necrosis (53% v 32%; P = .074).

CONCLUSION

This new histopathologic analysis technique for the evaluation of neoadjuvant chemotherapy effectiveness (which does not rely on tumor volume for its assessment) is a valuable prognostic indicator for patients with Ewing's sarcoma treated with surgery. Based on this preliminary report, cases of grade I or II chemotherapeutic tumor response should be considered clinical failures and a different, more aggressive postoperative chemotherapy regimen should be considered.
Localized but unresectable neuroblastoma: treatment and outcome of 145 cases. Italian Cooperative Group for Neuroblastoma.
Authors: Garaventa A , De Bernardi B , Pianca C , Donfrancesco A , Cordero di Montezemolo L , Di Tullio M T , Bagnulo S , Mancini A , Carli M , Pession A
Published: February 2017

PURPOSE

To define factors that influence outcome in children with localized but unresectable neuroblastoma by retrospective investigation of response to therapy and outcome in 21 Italian institutions.

PATIENTS AND METHODS

Of 145 assessable children diagnosed between 1979 and 1990, 77 were treated between 1979 and 1984 with three consecutive standard-dose (SD) protocols, and 68 between 1985 and 1990 with a high-dose (HD) protocol. All protocols included chemotherapy, followed by resection of primary tumor if feasible. If at least partial resection was achieved, consolidation therapy followed, except that from 1985 onward, patients considered disease-free following surgery received no further treatment.

RESULTS

Ninety-four of 145 patients (65%) achieved a complete response (CR) or partial response (PR) with chemotherapy and 75 (52%) subsequently underwent complete resection of the primary tumor. Eighty-one patients are alive (73 without disease, eight with disease), 63 have died, and one is lost to follow-up. The 5-year overall survival (OS) rate is 55% and progression-free survival (PFS) rate 50%. Both OS and PFS correlated with response to chemotherapy, removal of primary tumor, HD therapy, and serum lactate dehydrogenase (LDH) levels. Infants (< 1 year), independent of primary tumor site, and children aged 1 to 15 years with a nonabdominal primary tumor, did better compared with children aged 1 to 15 years with an abdominal primary tumor (PFS, 72% and 64% v 30%; P < .001 and < .01, respectively). Outcome of this last group improved with the HD protocol (PFS, 40% v 23%; P = .01).

CONCLUSION

In children with unresectable neuroblastoma, risk categories can be defined by age and primary tumor site. HD chemotherapy should be investigated for the poor-risk category age 1 to 15 years with an abdominal primary tumor.