bluuebunny/crossref_metadata_2025 huggingface dataset:
Reappraisal of the clinical and biologic significance of myeloid-associated antigen expression in childhood acute lymphoblastic leukemia.
Authors: Pui C H , Rubnitz J E , Hancock M L , Downing J R , Raimondi S C , Rivera G K , Sandlund J T , Ribeiro R C , Head D R , Relling M V , Evans W E , Behm F G
Published: February 2017

PURPOSE

To reassess the clinical and biologic significance of myeloid-associated antigen expression in childhood acute lymphoblastic leukemia (ALL).

PATIENTS AND METHODS

We prospectively studied 334 newly diagnosed cases of this disease, using a comprehensive panel of antibodies that represented five myeloid cluster groups (CD13, CD14, CD15, CD33, and CD65). Blast cells were tested for ETV6 and MLL rearrangement using Southern blot analysis.

RESULTS

CD13 was expressed in 13.7% of cases, CD14 in 1%, CD15 in 6.6%, CD33 in 16%, and CD65 in 9.7%. Approximately one third of cases (31.4%) expressed one or more of these antigens (B-cell precursor, 31.9%; T-cell, 28.8%), while 10.5% expressed two or more (B-cell precursor, 11.3%; T-cell, 6.1%). Among the B-cell precursor leukemias, myeloid-associated antigen expression was significantly associated with a lack of hyperdiploidy and rearrangements of ETV6 or MLL gene. Most of the cases with MLL rearrangements (82%) expressed CD65, CD15, and CD33, either alone or in combination, whereas 48% of those with a rearranged ETV6 gene expressed CD13, CD33, or both. Myeloid-associated antigen expression did not correlate with event-free survival, whether the analysis was based on any of the five antigens in our panel or on the three more commonly tested antigens (CD13, CD33, and CD65). Importantly, this finding was not affected by exclusion of patients with ETV6 or MLL gene rearrangements.

CONCLUSION

Even though blast cell expression of myeloid-associated antigen expression shows significant associations with specific genetic abnormalities, it lacks prognostic value in childhood ALL.
Hyper-CVAD and high-dose methotrexate/cytarabine followed by stem-cell transplantation: an active regimen for aggressive mantle-cell lymphoma.
Authors: Khouri I F , Romaguera J , Kantarjian H , Palmer J L , Pugh W C , Korbling M , Hagemeister F , Samuels B , Rodriguez A , Giralt S , Younes A , Przepiorka D , Claxton D , Cabanillas F , Champlin R
Published: February 2017

PURPOSE

Diffuse and nodular forms of mantle-cell lymphoma (MCL) are consistently associated with poor prognosis. In an effort to improve the outcome, we adopted a treatment plan that consisted of four courses of fractionated cyclophosphamide (CY) 1,800 mg/m2 administered with doxorubicin (DOX), vincristine (VCR), and dexamethasone (Hyper-CVAD) that alternated with high-dose methotrexate (MTX) and cytarabine (Ara-C). After four courses, patients were consolidated with high-dose CY, total-body irradiation, and autologous or allogeneic blood or marrow stem-cell transplantation.

PATIENTS AND METHODS

Forty-five patients were enrolled; 25 patients were previously untreated, 43 patients had Ann Arbor stage IV disease, and 42 patients had marrow involvement. Forty-one patients had diffuse histology, two patients had nodular, and two patients had blastic variants.

RESULTS

Hyper-CVAD/MTX-Ara-C induced a response rate of 93.5% (complete response [CR], 38%; partial response [PR], 55.5%) after four cycles of pretransplantation induction chemotherapy. All patients who went on to undergo transplantation achieved CRs. For the 25 previously untreated patients, the overall survival (OS) and event-free survival (EFS) rates at 3 years were 92% (95% confidence interval [CI], 80 to 100) and 72% (95% CI, 45 to 98) compared with 25% (95% CI, 12 to 62; P = .005) and 17% (95% CI, 10 to 43; P = .007), respectively, for the previously treated patients. When compared with a historic control group who received a CY, DOX, VCR, and prednisone (CHOP)-like regimen, untreated patients in the study had a 3-year EFS rate of 72% versus 28% (P = .0001) and a better OS rate (92% v 56%; P = .05). Treatment-related death occurred in five patients: all were previously treated and two received allogeneic transplants.

CONCLUSION

The Hyper-CVAD/MTX-Ara-C program followed by stem-cell transplantation is a promising new therapy for previously untreated patients with MCL.
Ongoing somatic mutations and clonal expansions after cure of Helicobacter pylori infection in gastric mucosa-associated lymphoid tissue B-cell lymphoma.
Authors: Thiede C , Alpen B , Morgner A , Schmidt M , Ritter M , Ehninger G , Stolte M , Bayerdörffer E , Neubauer A
Published: February 2017

PURPOSE

Although most patients with primary gastric low-grade mucosa-associated lymphoid tissue (MALT) B-cell lymphoma experience complete endoscopic and histologic remission after the cure of Helicobacter pylori infection, in many patients, the polymerase chain reaction (PCR) still detects monoclonal B cells in the gastric mucosa. The present study asked whether the lymphoma immunoglobulin VH (IgVH) sequences remained stable in patients with gastric MALT lymphoma after H pylori eradication.

PATIENTS AND METHODS

Eight patients with stage EI disease treated with H pylori eradication were analyzed before and at different time points after the cure of the infection. After the amplification of IgVH genes from DNA extracted from gastric biopsy specimens, monoclonal PCR products were cloned and multiple clones (43 to 105) were sequenced per patient.

RESULTS

Mutations were detected in all lymphoma VH sequences, which suggested germinal center or postgerminal center origin of the lymphoma B cells. In five of the eight patients, clonal heterogeneity was observed at diagnosis or during follow-up. Genealogical analysis of shared and unshared mutations showed that the process of somatic mutations was ongoing after H pylori eradication in four of the five patients who showed clonal instability. Ongoing mutations were observed in three of the four patients who completely responded to H pylori eradication, but in only one of the four patients who did not respond or who partially responded.

CONCLUSION

In low-grade gastric MALT lymphomas, an ongoing process of somatic hypermutation and antigen selection can be detected after the therapeutic removal of the underlying stimulus H pylori. These data point to the relevance of yet unknown antigens that drive this disease. In addition, they challenge the view that these lymphomas may be cured solely by the eradication of H pylori.
Neuroblastoma and treatment-related myelodysplasia/leukemia: the Memorial Sloan-Kettering experience and a literature review.
Authors: Kushner B H , Cheung N K , Kramer K , Heller G , Jhanwar S C
Published: February 2017

PURPOSE

To assess treatment-related myelodysplasia/leukemia (t-AML) in neuroblastoma patients by a review of the Memorial Sloan-Kettering Cancer Center (MSKCC) data and the literature.

PATIENTS AND METHODS

We studied 380 previously untreated and treated MSKCC patients. Low-risk patients received no cytotoxic therapy. High-risk patients received the N4, N5, or N6 regimens. Dosing per cycle and cumulative dosing of leukemogenic agents peaked with N6, which included four cycles of cyclophosphamide 4,200 mg/m2 and doxorubicin 75 mg/m2, plus three cycles of cisplatin 200 mg/m2 and etoposide 600 mg/m2. We reviewed the literature.

RESULTS

t-AML occurred in six MSKCC patients, which included three of 53 patients in whom the only chemotherapy consisted of N6, and three patients treated for relapsed or refractory neuroblastoma; no case of leukemia emerged among the 50 low-risk patients. Four cases were found incidentally in routine follow-up bone marrow tests. The 36-month cumulative incidence of t-AML in the N6 cohort was 7% (95% confidence interval, 0 to 15). Published data parallel the MSKCC experience in that t-AML after neuroblastoma was once rare but has become less so since the mid-1980s, when the intensified use of topoisomerase-II inhibitors and alkylators first gained wide acceptance and produced better response rates and longer survival.

CONCLUSION

Neuroblastoma itself is not associated with a host susceptibility to leukemia. However, current neuroblastoma treatment programs that use high-dose cyclophosphamide, cisplatin, and topoisomerase-II inhibitors may entail a considerable risk for t-AML. The incidence of t-AML in neuroblastoma patients may be underestimated because treatment and clinical factors can mask its presence. Efforts to devise effective but less leukemogenic treatment for neuroblastoma or to truncate leukemogenic therapy, eg, by exploiting molecular techniques for the early identification of complete remission, are warranted.
Current use of bisphosphonates in oncology. International Bone and Cancer Study Group.
Authors: Body J J , Bartl R , Burckhardt P , Delmas P D , Diel I J , Fleisch H , Kanis J A , Kyle R A , Mundy G R , Paterson A H , Rubens R D
Published: February 2017

PURPOSE

The purpose of this article is to review the recent data on bisphosphonate use in oncology and to provide some guidelines on the indications for their use in cancer patients.

DESIGN

The group consensus reached by experts on the rationale for the use of bisphosphonates in cancer patients and their current indications for the treatment of tumor-induced hypercalcemia and metastatic bone pain in advanced disease and for the prevention of the complications of multiple myeloma and of metastatic bone disease are reviewed.

RESULTS

Bisphosphonates are potent inhibitors of tumor-induced osteoclast-mediated bone resorption. They now constitute the standard treatment for cancer hypercalcemia, for which we recommend a dose of 1,500 mg of clodronate or 90 mg of pamidronate; the latter compound is more potent and has a longer lasting effect. Intravenous bisphosphonates exert clinically relevant analgesic effects in patients with metastatic bone pain. Regular pamidronate infusions can also achieve a partial objective response by conventional International Union Against Cancer criteria and enhance the objective response rate to chemotherapy. In breast cancer, the prolonged administration of oral clodronate 1,600 mg daily reduces the frequency of morbid skeletal events by more than one fourth, whereas monthly pamidronate infusions of 90 mg for only 1 year in addition to chemotherapy reduce by more than one third the frequency of all skeletal-related events. The use of bisphosphonates to prevent bone metastases remains experimental. Last, bisphosphonates in addition to chemotherapy are superior to chemotherapy alone in patients with stages II and III multiple myeloma and can reduce the skeletal morbidity rate by approximately one half.

CONCLUSION

Bisphosphonate use is a major therapeutic advance in the management of the skeletal morbidity caused by metastatic breast cancer or multiple myeloma, although many questions remain unanswered, notably regarding the optimal selection of patients and the duration of treatment.
Effective biomodulation by leucovorin of high-dose infusion fluorouracil given as a weekly 24-hour infusion: results of a randomized trial in patients with advanced colorectal cancer.
Authors: Köhne C H , Schöffski P , Wilke H , Käufer C , Andreesen R , Ohl U , Klaasen U , Westerhausen M , Hiddemann W , Schott G , Harstick A , Bade J , Horster A , Schubert U , Hecker H , Dörken B , Schmoll H J
Published: February 2017

PURPOSE

To determine whether high-dose infusional fluorouracil (FU) is effectively modulated by leucovorin (LV), interferon (IFN) alpha-2b, or both when given to patients with metastatic colorectal cancer.

PATIENTS AND METHODS

Patients (n = 236) with progressive, measurable disease were randomized to three groups and received FU 2,600 mg/m2 as a 24-hour continuous infusion (CI) weekly for 6 weeks with 2 weeks rest (FU24h) and LV 500 mg/m2 as a 2-hour infusion before FU or IFN 3 x 10(6) U subcutaneously 3 times weekly or both. Treatment continued until progressive disease or unacceptable toxicity was observed. Pairs of treatment arms were analyzed sequentially to detect equivalence or a 25% difference in response rates.

RESULTS

The rate of objective remission in patients who received FU24h/LV (44%; 40 of 91) was significantly higher than in patients who received FU24h/IFN (18%; 16 of 90; P < .05). The response rates of patients who received FU24h/LV versus FU24h/LV/IFN (27%; 13 of 49) were statistically equivalent. Significant differences were observed for time to tumor progression (TTP) (FU24h/LV, 7.1 months; FU24h/IFN, 3.9 months; FU24h/LV/IFN, 6.3 months; global P value < .009) and survival (16.6 months, 12.7 months, 19.6 months, respectively; global P value < .04). Unpredictable and life-threatening toxicity in the FU24h/LV/IFN arm required dose reduction of FU to 2,000 mg/m2/day and early stoppage of this arm. Toxicity was manageable in patients who received both FU24h/LV (grade 3 to 4 diarrhea, 21%) and FU24h/IFN (grade 3 to 4 diarrhea, 15%).

CONCLUSION

Response rate, TTP, and overall survival were superior for LV-containing regimens compared with IFN modulation alone. The addition of IFN to high-dose infusional FU plus LV offers no advantage and may increase toxicity. The regimen of high-dose infusional FU24h/LV warrants further evaluation in patients with metastatic colorectal cancer.
Confirmation that chromosome 18q allelic loss in colon cancer is a prognostic indicator.
Authors: Ogunbiyi O A , Goodfellow P J , Herfarth K , Gagliardi G , Swanson P E , Birnbaum E H , Read T E , Fleshman J W , Kodner I J , Moley J F
Published: February 2017

PURPOSE

Recent studies suggest that allelic loss of sequences from the long arm of chromosome 18 may be a useful prognostic indicator in colorectal cancer. The aim of the present study was to confirm whether 18q loss of heterozygosity (LOH) is of prognostic value in patients with colon cancer.

METHODS

Genomic DNA was prepared from archival tumor and corresponding normal tissue specimens from 151 patients who had undergone potentially curative surgery for adenocarcinoma of the colon. Polymerase chain reaction (PCR) was used to assess allelic loss of five chromosome 18q microsatellite markers in the tumors. The relationship between allelic loss and disease-free and disease-specific survival was investigated.

RESULTS

LOH was detected in 67 of 126 tumors. Chromosome 18q allelic loss was a negative prognostic indicator of both disease-free (relative risk [RR], 1.65; P = .01) and disease-specific survival (RR, 2.0; P = .003). 18q loss was also associated with significantly reduced disease-free and disease-specific survival in patients with stage II (P = .05 and P = .0156) and III (P = .038 and P = .032) disease.

CONCLUSION

Chromosome 18q allelic loss is a prognostic marker in colorectal cancers. Chromosome 18 LOH studies may be useful in identifying patients with stage II disease who are at high risk for recurrence, and as such might benefit from adjuvant chemotherapy.
Epoetin beta in the treatment of anemia in patients with advanced gastrointestinal cancer.
Authors: Glimelius B , Linné T , Hoffman K , Larsson L , Svensson J H , Näsman P , Svensson B , Helmers C
Published: February 2017

PURPOSE

The possibility that epoetin beta (EPO) could increase hemoglobin (B-Hb) levels and improve quality of life (QoL) in patients with advanced gastrointestinal cancers was investigated.

PATIENTS AND METHODS

One hundred patients with gastric, pancreatic, biliary, or colorectal cancers and subnormal B-Hb levels were included in a randomized study to test low-dose EPO (2,000 U subcutaneously thrice weekly [2,000 group]) against a higher dose (10,000 U times three [10,000 group]). Eighty-four patients were treated with chemotherapy. QoL was evaluated using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 instrument.

RESULTS

At baseline, mean B-Hb was 108 g/L with no difference between the groups. In the 10,000 group, an increase in B-Hb (>10 g/L) was seen in 30 (73%) patients treated with chemotherapy, after a median of 4 weeks, whereas a corresponding increase in the 2,000 group was seen in 15 (30%) patients after a median of 10 weeks (P < .001). A difference in the proportion of responders (five of eight v one of eight) was also seen in the group of patients not treated with chemotherapy. The proportion of responders was independent of baseline endogenous serum EPO level or observed/predicted log10 serum (S)-EPO levels. Patients who demonstrated improved B-Hb levels also showed improvements in QoL parameters. Tumor response was usually also associated with QoL improvements.

CONCLUSION

Treatment with EPO at a dose of 10,000 U thrice weekly can rapidly and safely increase B-Hb levels in a high proportion of patients with advanced gastrointestinal cancers. QoL is influenced by the B-Hb increase, but also by the course of the underlying malignancy. It is therefore difficult to define clearly the clinical relevance of the B-Hb increase as such.
Telomerase activity in pleural effusions: diagnostic significance.
Authors: Yang C T , Lee M H , Lan R S , Chen J K
Published: February 2017

PURPOSE

To determine the diagnostic value of pleural fluid telomerase activity in distinguishing a malignant from a nonmalignant pleurol effusion in a cohort of patients undergoing thoracentesis.

PATIENTS AND METHODS

Using a polymerase chain reaction (PCR)-based assay, telomerase activity was examined in the pleural fluid cells obtained from 144 consecutive, unselected patients. According to the final diagnosis achieved, these patients were classified into three groups: group I consisted of 70 malignant pleural effusions diagnosed by either fluid cytology or pleural biopsy, group II consisted of 52 nonmalignant pleural effusions, and another 22 samples were categorized to be suspicious malignant pleural effusions (group III) due to inconclusive results in effusion cytology and percutaneous pleural biopsy, but were strongly suspicious in clinical settings.

RESULTS

The presence of telomerase activity was observed in 64 of 70 samples in group I (91.4%), three of 52 samples in group II (5.8%), and 20 of 22 samples in group III. All three nonmalignant, telomerase-positive pleural effusion samples in group II were obtained from patients with tuberculosis. As a diagnostic criterion for malignant pleural effusion in group I and group II patients, positive telomerase activity had a sensitivity of 91.4%, a specificity of 94.2%, and a positive and negative predictive value of 0.96 and 0.89, respectively.

CONCLUSION

Our results indicate that the detection of telomerase activity may be a useful adjunct to cytopathologic methods in the diagnosis of malignant pleural effusions.
Plasma concentrations and pharmacokinetics of dimethylsulfoxide and its metabolites in patients undergoing peripheral-blood stem-cell transplants.
Authors: Egorin M J , Rosen D M , Sridhara R , Sensenbrenner L , Cottler-Fox M
Published: February 2017

PURPOSE

Dimethylsulfoxide (DMSO) is used to cryopreserve hematopoietic stem cells and is obligatorily infused into patients who receive stem-cell transplants. This study characterized the plasma concentrations and pharmacokinetics of DMSO and its metabolites in patients who underwent peripheral-blood stem-cell transplants.

MATERIALS AND METHODS

Plasma concentrations of DMSO, dimethylsulfone (DMSO2), and dimethylsulfide (DMSH2) were assessed in 10 patients who underwent autologous transplants with stem cells, cryopreserved in 10% DMSO (vol/vol). Blood was sampled at multiple times after the stem-cell infusion. Urine was pooled during the 24 hours postinfusion. DMSO, DMSO2, and DMSH2 were assayed simultaneously by gas chromatography. A one-compartment model with saturable elimination proved most suitable for fitting plasma DMSO concentration-versus-time data.

RESULTS

Stem-cell volumes infused ranged between 180 and 585 mL (254 to 824 mmol DMSO). Infusions lasted between 20 and 120 minutes. Peak plasma DMSO concentrations were 19.1 +/- 6.3 mmol/L (mean +/- SD). Pharmacokinetic parameters for volume of the central compartment (Vc), maximum velocity (Vmax), and Michaels-Menten constant (Km) were 37.3 +/- 17 L, 0.99 +/- 0.57 mmol/L/h, and 5.2 +/- 5.0 mmol/L, respectively. Plasma DMSO2 concentrations increased during the first 24 hours, plateaued at 4.4 +/- 1.2 mmol/L, and remained there until 48 hours (the last sample). DMSH2 concentrations were at steady-state by 5 minutes and remained between 3 and 5 mmol/L for 48 hours. Urinary excretion of DMSO and DMSO2 accounted for 44% +/- 4% and 4% +/- 1%, respectively, of the administered DMSO dose. Renal clearance of DMSO was 14.1 +/- 3.4 mL/min.

CONCLUSION

These data (1) document plasma concentrations of DMSO and metabolites in patients following peripheral-blood stem-cell transplants; (2) allow consideration of potential effects of these concentrations on stem-cell engraftment and drug-drug interactions; and (3) can facilitate a concentration-guided phase I trial of DMSO.
Lung cancer in young patients: analysis of a Surveillance, Epidemiology, and End Results database.
Authors: Ramalingam S , Pawlish K , Gadgeel S , Demers R , Kalemkerian G P
Published: February 2017

PURPOSE

A large community-based cancer registry was analyzed to determine if the clinicopathologic characteristics and/or survival rates of lung cancer patients under 50 years of age at diagnosis differ from those of patients 50 years of age or greater at diagnosis.

PATIENTS AND METHODS

Data regarding demographics, stage, histology, initial therapy, and survival were obtained on all patients with primary bronchogenic carcinoma registered in the metropolitan Detroit Surveillance, Epidemiology and End Results (SEER) registry from 1973 to 1992.

RESULTS

Of 31,266 patients, 9.0% were under 50 years of age at diagnosis. Females (40.1% v 31.2%; P < .001) and blacks (28.7% v 21.9%, P < .001) were overrepresented in the younger group compared with the older group. Younger patients had a significantly higher incidence of adenocarcinoma and were less likely to present with local-stage disease (18.6% v 25.2%; P < .001). Younger patients were significantly more likely to undergo surgery and/or combined-modality therapy. Relative survival at 5 years was significantly better in the younger group (16.1% v 13.4%; P < .001), mainly because of better survival in patients with local-stage disease (48.7% v 35.4%; P < .001). In a multivariate analysis, advanced-stage, nonsurgical initial therapy, age 50 years or greater at diagnosis, and male gender were independent negative prognostic factors.

CONCLUSION

The overrepresentation of females and blacks in the group of younger patients with lung cancer suggests an increased susceptibility to lung carcinogens in these populations. Overall, this study suggests that lung cancer is not a more aggressive disease in younger patients and that all patients with lung cancer should be managed along the same therapeutic guidelines.
Predictive factors of histologic response to primary chemotherapy in osteosarcoma of the extremity: study of 272 patients preoperatively treated with high-dose methotrexate, doxorubicin, and cisplatin.
Authors: Bacci G , Ferrari S , Delepine N , Bertoni F , Picci P , Mercuri M , Bacchini P , Brach del Prever A , Tienghi A , Comandone A , Campanacci M
Published: February 2017

PURPOSE

In osteosarcoma of the extremity, a strong correlation between chemotherapy-induced necrosis and prognosis has been reported. The aim of this study was to investigate the possible factors that influence histologic response to primary chemotherapy.

PATIENTS AND METHODS

In 272 patients with high-grade osteosarcoma of the extremity preoperatively treated with high-dose methotrexate (HDMTX), cisplatin (CDP), and doxorubicin (ADM), the histologic response to chemotherapy was evaluated and graded as complete (no viable tumor cells) or incomplete (persistence of viable tumor cells). Several factors, such as metastatic disease to the lung at diagnosis, sex, age, site and tumor volume, histologic subtype, serum alkaline phosphatase, lactate dehydrogenase (LDH), and methotrexate (MTX) pharmacokinetics were investigated to test their predictive significance on histologic response.

RESULTS

Fifty-one patients with localized disease (20.6%) and none of the 25 patients with metastatic disease at presentation had a complete histologic response (P = .006). After multivariate analysis, performed on patients with localized disease only, MTX serum peak (> or = 700 micromol/L) and histologic subtype were proven to be significant predictive factors of histologic response. A complete response was seen in 28.8% of patients with 700 micromol/L or greater MTX serum levels and in 9.9% of those patients with lower levels (P = .001). The chondroblastic subtype was less responsive (6.1% of complete response), compared with the osteoblastic (16.3%), fibroblastic (33.3%), and telangiectatic (42.3%).

CONCLUSION

Patients with metastatic osteosarcoma and localized chondroblastic osteosarcoma have a reduced chemosensitivity to primary chemotherapy with MTX, CDP, and ADM. MTX serum peak significantly influences tumor necrosis. A dose adaptation of MTX is recommended to obtain a serum peak of 700 micromol/L or greater when MTX is infused in 6 hours.
Oral tongue cancer in patients less than 45 years old: institutional experience and comparison with older patients.
Authors: Siegelmann-Danieli N , Hanlon A , Ridge J A , Padmore R , Fein D A , Langer C J
Published: February 2017

PURPOSE

To evaluate the demographics, differential risk profile, and treatment outcome in patients with squamous cell carcinomas (SCCs) of the oral tongue according to age at diagnosis.

PATIENTS AND METHODS

Patients with invasive SCC of the oral tongue who presented during the years 1985 to 1996 were identified using institutional tumor registry data. Demographics and clinical and pathologic characteristics were abstracted from the medical charts.

RESULTS

Eighty-eight patients were identified; 87 were included for analysis. Thirty patients were diagnosed at < or = 45 years of age and 57 at > or = 46 years. The groups showed comparable American Joint Committee on Cancer (AJCC) staging and male predominance. Prior exposure to tobacco and/or alcohol was noted in 40% and 82% of younger and older patients, respectively (P < .001); multiple smoking-related cancers occurred only in older patients (24.5% of older patients, P < .001). With median follow-up time of 29 months (younger group) and 21 months (older group), there were no significant differences in relapse rates, cancer-free survival (CFS), and overall survival (OS) rates (actuarial 5-year CFS rate, 48% and 54% in the younger and older patients, respectively; P = .91). Grouping patients according to smoking and/or alcohol history showed a trend toward better CFS in those with prior exposure to tobacco or alcohol compared with those with neither (5-year CFS rate, 60% and 38%, respectively, P = .11). In a multivariate analysis of all patients, with age used as a continuous parameter, only stage predicted CFS (P = .0019); for patients treated surgically with curative intent, only risk group predicted CFS (P = .0369).

CONCLUSION

Prognosis of oral tongue SCC was not affected by age at diagnosis. CFS rates tended to be worse in cases not related to prior tobacco or alcohol exposure. Multiple smoking-related cancers occurred only in older patients.
Multicenter outcome study of cancer patients admitted to the intensive care unit: a probability of mortality model.
Authors: Groeger J S , Lemeshow S , Price K , Nierman D M , White P , Klar J , Granovsky S , Horak D , Kish S K
Published: February 2017

PURPOSE

To develop prospectively and validate a model for probability of hospital survival at admission to the intensive care unit (ICU) of patients with malignancy.

PATIENTS AND METHODS

This was an inception cohort study in the setting of four ICUs of academic medical centers in the United States. Defined continuous and categorical variables were collected on consecutive patients with cancer admitted to the ICU. A preliminary model was developed from 1,483 patients and then validated on an additional 230 patients. Multiple logistic regression modeling was used to develop the models and subsequently evaluated by goodness-of-fit and receiver operating characteristic (ROC) analysis. The main outcome measure was hospital survival after ICU admission.

RESULTS

The observed hospital mortality rate was 42%. Continuous variables used in the ICU admission model are PaO2/FiO2 ratio, platelet count, respiratory rate, systolic blood pressure, and days of hospitalization pre-ICU. Categorical entries include presence of intracranial mass effect, allogeneic bone marrow transplantation, recurrent or progressive cancer, albumin less than 2.5 g/dL, bilirubin > or = 2 mg/dL, Glasgow Coma Score less than 6, prothrombin time greater than 15 seconds, blood urea nitrogen (BUN) greater than 50 mg/dL, intubation, performance status before hospitalization, and cardiopulmonary resuscitation (CPR). The P values for the fit of the preliminary and validation models are .939 and .314, respectively, and the areas under the ROC curves are .812 and .802.

CONCLUSION

We report a disease-specific multivariable logistic regression model to estimate the probability of hospital mortality in a cohort of critically ill cancer patients admitted to the ICU. The model consists of 16 unambiguous and readily available variables. This model should move the discussion regarding appropriate use of ICU resources forward. Additional validation in a community hospital setting is warranted.
Cost-effectiveness of routine radiation therapy following conservative surgery for early-stage breast cancer.
Authors: Hayman J A , Hillner B E , Harris J R , Weeks J C
Published: February 2017

PURPOSE

To examine the cost-effectiveness of radiation therapy following conservative surgery for early-stage breast cancer.

METHODS

Using a Markov model, a cost-utility analysis was performed to compare a strategy of radiation therapy versus no radiation therapy in a hypothetical cohort of 60-year-old women following conservative surgery. Local recurrence, distant recurrence, and survival rates used in the model were derived from randomized trial data. Utilities for the nonmetastatic health states were collected from actual patients. Direct medical costs were estimated using data from a single institution. Transportation and time costs were also estimated. Years of life, quality-adjusted life-years (QALYs), costs, and incremental cost/QALY over a 10-year time horizon were calculated by the model for each strategy.

RESULTS

The addition of radiation therapy results in a cost increase of $9,800 per patient, no change in life expectancy, and an increase of 0.35 QALYs per patient, which leads to an incremental cost-effectiveness ratio of $28,000/QALY, which is well below $50,000/QALY, a commonly cited threshold for cost-effective care. Sensitivity analysis shows the ratio to be heavily influenced by the cost of radiation therapy and the quality-of-life benefit that results from decreased risk of local recurrence.

CONCLUSION

Radiation therapy following conservative surgery is cost-effective compared with other accepted medical interventions. This study illustrates the importance of considering an intervention's effect on quality of life, as well as survival in defining cost-effectiveness.
Phase II study of irinotecan combined with cisplatin in patients with previously untreated small-cell lung cancer. West Japan Lung Cancer Group.
Authors: Kudoh S , Fujiwara Y , Takada Y , Yamamoto H , Kinoshita A , Ariyoshi Y , Furuse K , Fukuoka M
Published: February 2017

PURPOSE

Irinotecan (CPT-11) is effective against small-cell lung cancer (SCLC) as monotherapy. Cisplatin is also a key drug against SCLC. We conducted a phase II study of CPT-11 combined with cisplatin to evaluate the efficacy and toxicity of this regimen in patients with previously untreated SCLC.

PATIENTS AND METHODS

Seventy-five patients with previously untreated SCLC were enrolled onto the study. CPT-11 60 mg/m2 was administered intravenously on days 1, 8, and 15 in combination with cisplatin 60 mg/m2 on day 1 every 28 days. Four courses of chemotherapy followed by thoracic irradiation were given to patients with limited disease (LD) and six courses to patients with extensive disease (ED).

RESULTS

The overall response rate was 84%, with a complete response (CR) rate of 29%. Forty patients with LD achieved an overall response rate of 83% and a CR rate of 30% and 35 patients with ED achieved an overall response rate of 86% and a CR rate of 29%. The median response duration was 8.0 months for LD patients and 6.6 months for ED patients. The median survival was 14.3 months for LD patients and 13.0 months for ED patients. The major grade 3 or 4 toxicities were neutropenia (77%), leukopenia (45%), diarrhea (19%), and anemia (39%). Two patients died with concomitant neutropenia and diarrhea.

CONCLUSION

This is a new active regimen for SCLC, especially ED-SCLC, with acceptable toxicity. A phase III study that compares CPT-11/cisplatin with etoposide/cisplatin for ED-SCLC is now being conducted.
Prognostic factors for survival of patients treated systemically for disseminated melanoma.
Authors: Eton O , Legha S S , Moon T E , Buzaid A C , Papadopoulos N E , Plager C , Burgess A M , Bedikian A Y , Ring S , Dong Q , Glassman A B , Balch C M , Benjamin R S
Published: February 2017

PURPOSE

The current American Joint Commission on Cancer (AJCC) staging system distinguishes between soft tissue and visceral metastases in advanced (stage IV) melanoma. We sought to verify these staging criteria and to identify prognostic variables that could be used to evaluate the impact of systemic therapy on long-term survival during the prior decade.

PATIENTS AND METHODS

We conducted a retrospective study of patients with advanced cutaneous melanoma enrolled in clinical trials between 1979 and 1989 at The University of Texas M.D. Anderson Cancer Center. Pretreatment age, sex, number of organs with metastases, serum levels of lactate dehydrogenase (LDH) and albumin, and period of enrollment were analyzed using a Cox proportional hazards model of survival.

RESULTS

In univariate and multivariate analyses that involved 318 stage IV patients, normal serum levels of LDH and albumin, soft tissue and/or single visceral organ metastases (especially lung), female sex, and enrollment late in the decade were independent positive predictors for survival. In multivariate analyses, the current AJCC criteria did not significantly predict outcome. Systemic treatment response did not bias these results, and only 4% of patients had a complete response. Patients who lived more than 2 years (11%) had a mix of favorable prognostic characteristics and a high frequency of systemic or surgically induced complete response.

CONCLUSION

This study supports the use of stratification parameters that reflect the favorable prognostic impact of soft tissue or single visceral organ metastases and normal serum levels of LDH and albumin at time of enrollment in advanced melanoma trials. Improved survival over the prior decade probably reflects advances in diagnostic and palliative interventions.
Health-related quality of life in the general Norwegian population assessed by the European Organization for Research and Treatment of Cancer Core Quality-of-Life Questionnaire: the QLQ=C30 (+ 3).
Authors: Hjermstad M J , Fayers P M , Bjordal K , Kaasa S
Published: February 2017

PURPOSE

To obtain reference data on health-related quality of life (HRQOL) for the functional and symptom scales and single items of the European Organization for Research and Treatment of Cancer Core Quality-of-Life Questionnaire (EORTC QLQ-C30 [+ 3]) in a representative sample of the Norwegian general population.

PATIENTS AND METHODS

A randomly selected sample of 3,000 people from the Norwegian population, aged 18 to 93 years, who represent geographic diversity, took part in this postal survey. The EORTC QLQ-C30 (+ 3) and a questionnaire about demographic data and health were sent by mail. A new questionnaire package was sent as a reminder after 3 weeks.

RESULTS

The survey yielded a high response rate with 1,965 of 2,892 eligible persons responding (68%). There was a low amount of missing data (1.8%). Internal consistency was highly satisfactory and yielded Cronbach's alpha coefficients greater than 0.70 for all but two functional scales and one symptom scale. The sensitivity of the questionnaire was shown by the excellent discrimination between age and sex groups. Clinical validity was shown by the distinct differences according to age and sociodemographic characteristics. Women reported lower functional status and global quality of life (mean scale scores from 71.7 to 91.0) than men (mean scale scores from 75.4 to 94.4), and also more symptoms and problems. This was remarkably consistent across age groups, as was a decline in functional status with an increase in age.

CONCLUSION

This is the first study that presented reference data from the EORTC QLQ-C30 (+ 3) in a sample from a general population and seems to provide valid measures of HRQOL within different age groups. The results may serve as a guideline for clinicians when interpreting HRQOL in their own groups of patients, and contributes to a better understanding of the significance of mean scores and their clinical relevance.
Effect of follicularity on autologous transplantation for large-cell non-Hodgkin's lymphoma.
Authors: Vose J M , Bierman P J , Lynch J C , Weisenburger D D , Kessinger A , Chan W C , Greiner T C , Armitage J O
Published: February 2017

PURPOSE

This study evaluated the outcomes of patients who received high-dose chemotherapy (HDC) and autologous hematopoietic stem-cell transplantation (ASCT) for large-cell non-Hodgkin's lymphoma (NHL) and the effect of a follicular versus a diffuse histology.

PATIENTS AND METHODS

The prognostic factors in 289 patients who underwent HDC and ASCT for large-cell NHL between May 1983 and December 1996 were analyzed.

RESULTS

With a median follow-up duration of 24 months for surviving patients (range, 3 to 131 months), 112 of 289 (39%) were alive and 82 of 289 (28%) were failure-free. In a multivariate analysis, the factors associated with a poorer failure-free survival (FFS) included a lactic dehydrogenase (LDH) level greater than normal (P < .0001), three or more prior chemotherapy regimens received (P < .01), a mass > or = 10 cm at transplant (P < .01), and diffuse histology at the time of transplant (P = .026). Patients who received HDC and ASCT for large-cell NHL in the good-prognosis category (normal LDH, < three prior chemotherapy regimens, no large mass, and not chemotherapy-resistant) had a 5-year survival rate of 45%. Within the good-prognosis group, patients with diffuse large-cell NHL had a 5-year survival rate of 42% compared with 58% for patients with follicular large-cell (FLC) lymphoma (P = .05).

CONCLUSION

Good-prognosis patients with FLC histology who receive HDC and ASCT have an improved survival compared with good-prognosis patients with a diffuse large-cell histology.
Response of children with high-risk acute lymphoblastic leukemia treated with and without cranial irradiation: a report from the Children's Cancer Group.
Authors: Nachman J , Sather H N , Cherlow J M , Sensel M G , Gaynon P S , Lukens J N , Wolff L , Trigg M E
Published: February 2017

PURPOSE

Intensified intrathecal (i.t.) chemotherapy without cranial radiation therapy (CRT) prevents CNS relapse in children with low-risk and intermediate-risk acute lymphoblastic leukemia (ALL). In the current study, high-risk ALL patients who achieved a rapid early response (RER) to induction chemotherapy were randomized to receive intensive systemic chemotherapy and presymptomatic CNS therapy that consisted of either i.t. methotrexate (MTX) and CRT or intensified i.t. MTX alone.

PATIENTS AND METHODS

Children (n = 636) with high-risk ALL (aged 1 to 9 years and WBC count > or = 50,000/microL or age > or = 10 years, excluding those with lymphomatous features) who achieved an RER (< or = 25% marrow blasts on day 7) to induction therapy and lacked CNS disease at diagnosis were randomized to receive systemic therapy with either i.t. MTX and CRT (regimen A, n = 317) or intensified i.t. MTX alone (regimen B, n = 319).

RESULTS

Interim analysis in July 1993 revealed 3-year event-free survival (EFS) estimates of 82.1% +/- 4.0% (SD)and 70.4% +/- 4.2% for patients treated on regimens A and B, respectively (P = .004). As of January 1996, outcome had changed: 5-year EFS estimates were 69.1% +/- 3.4% and 75.0% +/- 2.7% for regimens A and B, respectively (P = 0.50). Marrow relapses comprised 57 events on regimen A and 43 events on regimen B. Fewer late events occurred on regimen B.

CONCLUSION

For high-risk pediatric ALL patients who show an RER to induction therapy and are treated with systemic Children's Cancer Group (CCG)-modified Berlin-Frankfurt-Munster (BFM) chemotherapy, presymptomatic CNS therapy that consists of either i.t. MTX plus CRT or intensified i.t. MTX alone results in a similar 5-year EFS outcome. Furthermore, intensified i.t. MTX may protect against late bone marrow relapse.
Phase I study of topotecan in combination with cyclophosphamide in pediatric patients with malignant solid tumors: a Pediatric Oncology Group Study.
Authors: Saylors R L , Stewart C F , Zamboni W C , Wall D A , Bell B , Stine K C , Vietti T J
Published: February 2017

PURPOSE

To determine the maximum-tolerated dose (MTD) and dose-limiting toxicity of topotecan when combined with cyclophosphamide in pediatric patients with recurrent or refractory malignant solid tumors.

PATIENTS AND METHODS

A total of 33 patients received cyclophosphamide (250 mg/m2/dose) followed by topotecan in escalating doses (0.6 to 0.75 mg/m2/dose), each given as a 30-minute infusion daily for 5 days. A total of 154 fully assessable treatment courses were given to these patients.

RESULTS

Neutropenia was the dose-limiting toxicity of the therapy at both topotecan dose levels. The addition of filgrastim allowed escalation of the topotecan dose to the 0.75-mg/m2 level with acceptable neutropenia. Other significant toxicities were anemia and thrombocytopenia. Nonhematopoietic toxicity of grades > or = 3 was not observed. Responses were reported in patients with Wilms' tumor (one complete response [CR], one partial response [PR]), neuroblastoma (one CR, one PR), rhabdomyosarcoma (one PR), and osteosarcoma (one PR). Pharmacokinetic studies indicate that cyclophosphamide administered on the schedule used in this study did not alter topotecan disposition on day 5. As with previous studies, a pharmacodynamic relation between systemic exposure and myelosuppression was noted.

CONCLUSION

The combination of topotecan and cyclophosphamide shows activity in a wide variety of pediatric solid tumors and can be given with acceptable hematopoietic toxicity with the use of filgrastim support. We recommend that pediatric phase II trials use cyclophosphamide 250 mg/m2 followed by topotecan 0.75 mg/m2 daily for 5 days with filgrastim for amelioration of neutropenia.
Randomized comparison of cisplatin and etoposide and either bleomycin or ifosfamide in treatment of advanced disseminated germ cell tumors: an Eastern Cooperative Oncology Group, Southwest Oncology Group, and Cancer and Leukemia Group B Study.
Authors: Nichols C R , Catalano P J , Crawford E D , Vogelzang N J , Einhorn L H , Loehrer P J
Published: February 2017

PURPOSE

To compare standard therapy with bleomycin, etoposide, and cisplatin (BEP) to experimental therapy with etoposide, ifosfamide, and cisplatin (VIP) as primary treatment of men with advanced, disseminated germ cell tumors.

PATIENTS AND METHODS

A total of 304 men with advanced disseminated germ cell tumors were randomly allocated to receive four courses of BEP or VIP. Two hundred ninety-nine patients were assessable for toxicity and 286 were assessable for response. Complete response rates, favorable response (complete remission, surgical free of disease, continuous partial remission for 2+ years), time to treatment failure, and overall survival were assessed.

RESULTS

Overall complete remission rate (VIP, 37%; BEP, 31%), favorable response rate (VIP, 63%; BEP, 60%), failure-free at 2 years (VIP, 64%; BEP, 60%), and 2-year overall survival (VIP, 74%; BEP, 71%) were not significantly different between the two treatments. Grade 3 or worse toxicity, particularly hematologic and genitourinary toxicity, was significantly more common in patients who received VIP.

CONCLUSION

BEP and VIP produce comparable favorable response rate and survival in patients with poor-risk germ cell tumors. The substitution of ifosfamide for bleomycin, however, was associated with significantly greater toxicity. Four courses of BEP remain the standard treatment for advanced disseminated germ cell tumors.
Correlation of p34cdc2 cyclin-dependent kinase overexpression, CD44s downregulation, and HER-2/neu oncogene amplification with recurrence in prostatic adenocarcinomas.
Authors: Kallakury B V , Sheehan C E , Ambros R A , Fisher H A , Kaufman R P , Muraca P J , Ross J S
Published: February 2017

PURPOSE

To test whether p34cdc2 overexpression, CD44s downregulation, and HER-2/neu amplification correlate with disease recurrence after radical prostatectomy, and to evaluate a possible biologic association between p34cdc2 and HER-2/neu expression.

MATERIALS AND METHODS

Immunohistochemical (IHC) detection of both p34cdc2 cyclin-dependent kinase (CDK) and CD44s expression and fluorescence in situ hybridization (FISH)-based analysis of HER-2/neu gene status were performed on formalin-fixed, paraffin-embedded sections of 106 prostatic adenocarcinomas (PACs). Findings were correlated with Gleason grade, pathologic stage, DNA ploidy, and postsurgical biochemical disease recurrence.

RESULTS

CDK overexpression correlated with tumor grade (P = .001), DNA ploidy (P = .001), pathologic stage (P = .04), and disease recurrence (P = .01). CD44s downregulation correlated with grade (P = .03), ploidy (P = .01), and recurrence (P = .02). HER-2/neu amplification correlated with grade (P = .001), ploidy (P = .001), and recurrence (P = .01). On multivariate analysis, CDK overexpression independently predicted recurrence (P = .001) after prostatectomy. CDK expression correlated with HER-2/neu status with 32 of 65 (49%) tumors that overexpressed CDK and showed concomitant HER-2/neu amplification (P = .04).

CONCLUSION

This study showed that p34cdc2, CD44s, and HER-2/neu are variably expressed or amplified in prostatic carcinoma and that such alteration may affect tumor behavior. In addition, CDK overexpression and HER-2/neu amplification may be biologically related.