bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive Assessment of the Elderly Cancer Patient: The Feasibility of Self-Report Methodology
Authors: Ingram Sally S. , Seo Pearl H. , Martell Robert E. , Clipp Elizabeth C. , Doyle Martha E. , Montana Gustavo S. , Cohen Harvey J.
Published: February 2017

PURPOSE: Comprehensive geriatric assessment (CGA) has aided the medical community greatly in understanding the quality-of-life issues and functional needs of older patients. With its professional team assessment approach, however, CGA may be time consuming and costly. The goal of the present study was to assess the ability of cancer patients to complete a self-administered CGA and then to characterize cancer patients across multiple domains and age groups.

PATIENTS AND METHODS: Two hundred sixty-six male outpatient oncology patients at the Durham Veterans Affairs Medical Center were asked to fill out a survey assessing 10 domains (demographics, comorbid conditions, activities of daily living, functional status, pain, financial well being, social support, emotional state, spiritual well-being, and quality of life).

RESULTS: Seventy-six percent of the patients who received their surveys and kept their appointments returned the assessment tool. Older oncology patients had significantly less education (P < .0001), income (P = .05), frequent exercise (P = .01), and chance of being disease free (P = .003) than younger patients. Other findings in older patients were a higher rate of marriage (P = .02), more difficulty in taking medications (P = .05), and less cigarette (P = .03) and alcohol (P = .03) use. Members of all age cohorts reported a sense of social support, with younger patients deriving this more from family and friends than older patients, and older patients deriving social support more from membership in religious communities than younger patients. No differences were found across age groups for number and impact of comorbid illnesses, number of medications, basic and instrumental activities of daily living, pain, overall health rating, financial adequacy, anxiety, depression, and quality of life.

CONCLUSION: CGA can be conducted in an outpatient cancer community using a self-report format. Despite the fact that this population varied demographically across age groups and is limited to veterans, this study demonstrated remarkable similarities between younger and older cancer patients in terms of functional status, health states, and quality of life.
Phase II Study of Twice-Daily High-Dose Thoracic Radiotherapy Alternating With Cisplatin and Vindesine for Unresectable Stage III Non–Small-Cell Lung Cancer: Japan Clinical Oncology Group Study 9306
Authors: Sekine Ikuo , Nishiwaki Yutaka , Ogino Takashi , Yokoyama Akira , Saito Mari , Mori Kiyoshi , Tsukiyama Iwao , Tsuchiya Satoshi , Hayakawa Kazushige , Yoshimura Kimio , Ishizuka Naoki , Saijo Nagahiro
Published: February 2017

PURPOSE: To evaluate the efficacy and toxicity of high-dose thoracic radiotherapy (TRT) alternating with chemotherapy (CH) for unresectable stage III non–small-cell lung cancer (NSCLC).

PATIENTS AND METHODS: Forty-one patients received TRT with 1.5 Gy twice daily, 5 days a week, on weeks 1, 2, 5, 6, and 9, up to a total dose of 66 to 72 Gy, alternating with cisplatin 80 mg/m2 on day 1 and vindesine 3 mg/m2 on days 1 and 8, repeated every 4 weeks, for two or three courses beginning on week 3.

RESULTS: The median (range) total dose of TRT and number of CH courses were 72 Gy (16.5 to 72 Gy) and three (zero to three), respectively. Delay in TRT ≥ 5 days was observed in 24 (75%) of 32 patients who completed the projected treatment, due to leukopenia in 12, esophagitis in seven, infection in two, and other causes in three patients. Partial responses were obtained in 36 patients (88%). The median survival time and 3- and 5-year survival rates were 18.4 months, 24%, and 10%, respectively. Grade 3 or 4 leukopenia and esophagitis developed in 32 and seven patients, respectively. Grade 3 or 4 late esophageal toxicity developed in two patients.

CONCLUSION: Alternating high-dose TRT and CH for stage III NSCLC produced a high response rate with median and long-term survival comparable to prior trials utilizing standard approaches in this population. Acute and late esophageal toxicity was observed and interruption of TRT was required in most of the patients.
Communication Between Physicians and Older Women With Localized Breast Cancer: Implications for Treatment and Patient Satisfaction
Authors: Liang Wenchi , Burnett Caroline B. , Rowland Julia H. , Meropol Neal J. , Eggert Lynne , Hwang Yi-Ting , Silliman Rebecca A. , Weeks Jane C. , Mandelblatt Jeanne S.
Published: February 2017

PURPOSE: To identify factors associated with patient-physician communication and to examine the impact of communication on patients’ perception of having a treatment choice, actual treatment received, and satisfaction with care among older breast cancer patients.

MATERIALS AND METHODS: Data were collected from 613 pairs of surgeons and their older (≥ 67 years) patients diagnosed with localized breast cancer. Measures of patients’ self-reported communication included physician- and patient-initiated communication and the number of treatment options discussed. Logistic regression analyses were conducted to examine the relationships between communication and outcomes.

RESULTS: Patients who reported that their surgeons mentioned more treatment options were 2.21 times (95% confidence interval [CI], 1.62 to 3.01) more likely to report being given a treatment choice, and 1.33 times (95% CI, 1.02 to 1.73) more likely to get breast-conserving surgery with radiation than other types of treatment. Surgeons who were trained in surgical oncology, or who treated a high volume of breast cancer patients (≥ 75% of practice), were more likely to initiate communication with patients (odds ratio [OR] = 1.62; 95% CI, 1.02 to 2.56; and OR = 1.68; 95% CI, 1.01 to 2.76, respectively). A high degree of physician-initiated communication, in turn, was associated with patients’ perception of having a treatment choice (OR = 2.46; 95% CI, 1.29 to 4.70), and satisfaction with breast cancer care (OR = 2.13; 95% CI, 1.17 to 3.85) in the 3 to 6 months after surgery.

CONCLUSION: Greater patient-physician communication was associated with a sense of choice, actual treatment, and satisfaction with care. Technical information and caring components of communication impacted outcomes differently. Thus, the quality of cancer care for older breast cancer patients may be improved through interventions that improve communication within the physician-patient dyad.
Comparison of the Systemic and Intratumoral Effects of Tamoxifen and the Aromatase Inhibitor Vorozole in Postmenopausal Patients With Primary Breast Cancer
Authors: Harper-Wynne Catherine L. , Sacks Nigel P.M. , Shenton Karyn , MacNeill Fiona A. , Sauven Paul , Laidlaw Ian J. , Rayter Zen , Miall Stephanie , Howes Angela , Salter Janine , Hills Margaret J. , Lowe Frances M. , A’Hern Roger , Nasiri Nazar , Doody Debbie , Iqbal Jhangir , Dowsett Mitchell
Published: February 2017

PURPOSE: To determine biologic differences, if any, between presurgical endocrine treatment with an aromatase inhibitor (vorozole) and tamoxifen in patients with postmenopausal primary breast cancer.

PATIENTS AND METHODS: Randomization was to 12 weeks of 2.5 mg of vorozole per day or 20 mg of tamoxifen per day, both orally. Clinical response was assessed monthly together with serum sex hormone binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH), estrogens (E1, E2, and E1S), lipids, insulin-like growth factor-1 (IGF-1), and bone metabolites (CrossLaps CTx). Tissue samples for Ki67, apoptotic index (AI), estrogen receptor, and progesterone receptor were collected at 0, 2, and 12 weeks.

RESULTS: Ki67 fell by 58% and 43% (means) at 2 weeks in the vorozole and tamoxifen patients, respectively (P = .13). In the vorozole group, the correlations of proportional changes in Ki67 at 2 weeks with tumor volume changes and clinical response at 12 weeks were not significant (P = .09) and marginally significant (P = .04), respectively. Serum lipids did not differ between groups. Serum levels of EI, E2, and E1S were suppressed markedly by vorozole, whereas levels of SHBG increased and LH and FSH fell significantly with tamoxifen. IGF-1 levels fell significantly with tamoxifen (P = .001) compared with the nonsignificant rise with vorozole. Twelve-week CTx values fell by 19% with tamoxifen (P = .006) and rose by 11% with vorozole (P = .15).

CONCLUSION: The correlation with vorozole of Ki67 with volume and clinical response supports this as an intermediate marker. The nonsignificant effects on bone and lipid metabolism by the aromatase inhibitor may be important to consider for adjuvant and potential prevention strategies.
Quantitatively Determined Survivin Expression Levels Are of Prognostic Value in Human Gliomas
Authors: Chakravarti Arnab , Noll Elizabeth , Black Peter McL. , Finkelstein Daniel F. , Finkelstein Dianne M. , Dyson Nicholas J. , Loeffler Jay S.
Published: February 2017

PURPOSE: Survivin is a novel antiapoptotic gene that has been recently cloned and characterized. Its expression has been found to be of prognostic significance in several tumor types. This is the first study on the prognostic significance of survivin expression in human gliomas.

MATERIALS AND METHODS: We used quantitative Western blot analysis with densitometry to determine survivin protein expression levels in 92 glioma cases for which frozen tissue was available for analysis. Survivin positivity and expression levels were correlated with histopathologic features of the tumors, apoptosis (as measured by cleaved, or activated, caspase 3 levels), and clinical outcome.

RESULTS: Survivin expression has clear prognostic value in human gliomas. Patients with detectable survivin expression had significantly shorter overall survival times (P < .0001) compared with those without detectable expression when all glioma patients were considered. Although glioblastoma multiforme (GBM) patients had significantly higher rates of survivin positivity and higher levels of survivin expression (P < .0001) than their non-GBM counterparts, the prognostic value of survivin expression seemed to be independent of histology alone. Survivin-positive GBM patients had significantly shorter overall survival times compared with survivin-negative GBM patients (P < .0001). Likewise, survivin-positive non-GBM patients had shorter survival times compared with survivin-negative non-GBM patients (P = .029). Furthermore, increasing levels of survivin expression significantly correlated with reduced survival times when all glioma patients were considered, and markedly so for GBM patients (P < .0001). Increasing survivin levels significantly correlated with reduced expression of cleaved caspase 3, indicating its association with antiapoptotic activity.

CONCLUSION: Survivin positivity and protein expression levels, as determined quantitatively, are of significant prognostic value in human gliomas and seem to be associated with reduced apoptotic capacity of these tumors.
Loss of MDA-7 Expression With Progression of Melanoma
Authors: Ellerhorst Julie A. , Prieto Victor G. , Ekmekcioglu Suhendan , Broemeling Lyle , Yekell Sandra , Chada Sunil , Grimm Elizabeth A.
Published: February 2017

PURPOSE: Ectopic transfer of the melanoma differentiation-associated gene-7 (mda-7) has been shown in vitro to suppress growth and induce apoptosis in a variety of human tumor cell lines; similar effects are not elicited in normal cells. Thus, the mda-7 gene seems to function as a novel tumor suppressor, and there is interest in the potential of mda-7 gene transfer as cancer therapy. The objective of this study was to determine if MDA-7 protein is lost during primary melanoma progression from superficial to invasive stages and from localized to metastatic tumor. As a secondary objective, we analyzed MDA-7 protein expression in primary melanomas for correlation with predictors of outcome and with survival.

MATERIALS AND METHODS: MDA-7 protein expression was evaluated by immunohistochemistry in 41 primary melanomas and 41 metastases, including 24 paired samples. Each sample was scored for the percentage of positive cells and the overall intensity of immunolabeling.

RESULTS: Significant decreases in MDA-7 immunostaining, reflected in both number and intensity scores, were observed when comparing the intraepidermal and superficially invasive portions with the deeply invasive portions of primary tumors. Significant differences were also observed when comparing primary tumors to paired metastases.

CONCLUSION: Downregulation of MDA-7 expression in primary melanomas facilitates progression to invasive and metastatic stages. These data support the development of Ad-mda7 as gene therapy for advanced melanoma.
Weight Loss in Breast Cancer Patient Management
Authors: Chlebowski Rowan T. , Aiello Erin , McTiernan Anne
Published: February 2017

PURPOSE: To systematically review and summarize evidence relevant to obesity and breast cancer clinical outcome, potential hormonal mediating mechanisms, and the current status of weight loss interventions for chronic disease management.

METHODS: A comprehensive, formal literature review was conducted to identify 5,687 citations with key information from 159 references summarized in text and tables. This process included a search for all breast cancer studies exploring associations among survival or recurrence and obesity at diagnosis or weight gain after diagnosis using prospective criteria.

RESULTS: On the basis of observational studies, women with breast cancer who are overweight or gain weight after diagnosis are found to be at greater risk for breast cancer recurrence and death compared with lighter women. Obesity is also associated with hormonal profiles likely to stimulate breast cancer growth. Recently, use of weight loss algorithms proven successful in other clinical settings that incorporate dietary therapy, physical activity, and ongoing behavior therapy have been endorsed by the National Institutes of Health and other health agencies.

CONCLUSION: Although definitive weight loss intervention trials in breast cancer patients remain to be conducted, the current evidence relating increased body weight to adverse breast cancer outcome and the documented favorable effects of weight loss on clinical outcome in other comorbid conditions support consideration of programs for weight loss in breast cancer patients. Recommendations for the clinical care of overweight or obese breast cancer patients are offered.
Screening for Lung Cancer With Low-Dose Helical Computed Tomography: Anti-Lung Cancer Association Project
Authors: Sobue Tomotaka , Moriyama Noriyuki , Kaneko Masahiro , Kusumoto Masahiko , Kobayashi Toshiaki , Tsuchiya Ryosuke , Kakinuma Ryutaro , Ohmatsu Hironobu , Nagai Kanji , Nishiyama Hiroyuki , Matsui Eisuke , Eguchi Kenji
Published: February 2017

PURPOSE: Because efficacy of lung cancer screening using chest x-ray is controversial and insufficient, other screening modalities need to be developed. To provide data on screening performance of low-dose helical computed tomography (CT) scanning and its efficacy in terms of survival, a one-arm longitudinal screening project was conducted.

PATIENTS AND METHODS: A total of 1,611 asymptomatic patients aged 40 to 79 years, 86% with smoking history, were screened by low-dose helical CT scan, chest x-ray, and 3-day pooled sputum cytology with a 6-month interval.

RESULTS: At initial screening, the proportions of positive tests were 11.5%, 3.4%, and 0.8% with low-dose helical CT scan, chest x-ray, and sputum cytology, respectively. In 1,611 participants, 14 (0.87%) cases of lung cancer were detected, with 71% being stage IA disease and a mean tumor diameter of 19.8 mm. At repeated screening, the proportions of positive tests were 9.1%, 2.6%, and 0.7% with low-dose helical CT, chest x-ray, and sputum cytology, respectively. In 7,891 examinations, 22 (0.28%) cases of lung cancer were detected, with 82% being stage IA disease and a mean tumor diameter of 14.6 mm. The 5-year survival rate for screen-detected lung cancer was 76.2% and 64.9% for initial and repeated screening, respectively.

CONCLUSION: Screening with low-dose helical CT has potential to improve screening efficacy in terms of reducing lung cancer mortality. An evaluation of efficacy using appropriate methods is urgently required.
Phase II Trial of Weekly Paclitaxel in Patients With Previously Treated Advanced Urothelial Cancer
Authors: Vaughn David J. , Broome Catherine M. , Hussain Maha , Gutheil John C. , Markowitz Avi B.
Published: February 2017

PURPOSE: We evaluated the efficacy and toxicity of weekly paclitaxel in patients with previously treated advanced urothelial cancer.

PATIENTS AND METHODS: Patients with urothelial cancer who had received one prior systemic chemotherapy regimen for advanced disease and had evidence of disease progression were eligible for enrollment. Patients received paclitaxel 80 mg/m2 by 1-hour intravenous infusion weekly. A cycle of therapy consisted of four weekly treatments.

RESULTS: The study enrolled 31 patients. Mean age was 66 years, and 45% of patients had three or more involved metastatic sites. Only 26% of patients had responded to prior chemotherapy. The median number of cycles delivered was three (range, one to eight) at a mean weekly paclitaxel dose of 79 mg/m2. Three patients achieved a partial response (10%; 95% confidence interval, 0% to 20%). Median time to progression was 2.2 months, and median overall survival time was 7.2 months. Therapy was well tolerated with minimal hematologic toxicity. Grade 3 nonhematologic toxicities were also uncommon.

CONCLUSION: Although the overall response rate to weekly paclitaxel in patients with previously treated advanced urothelial cancer was modest, the chemotherapy-refractory nature of the study population should be considered.
Phase III Trial Comparing Radical Radiotherapy With and Without Cisplatin Chemotherapy in Patients With Advanced Squamous Cell Cancer of the Cervix
Authors: Pearcey R. , Brundage M. , Drouin P. , Jeffrey J. , Johnston D. , Lukka H. , MacLean G. , Souhami L. , Stuart G. , Tu D.
Published: February 2017

PURPOSE: To test the hypothesis that cisplatin (CDDP) administered concurrently with standard radiotherapy (RT) would improve pelvic control and survival in patients with advanced squamous cell cancer of the cervix.

PATIENTS AND METHODS: A total of 259 patients with International Federation of Gynecology and Obstetrics stage IB to IVA squamous cell cervical cancer with central disease ≥ 5 cm or histologically confirmed pelvic lymph node involvement were randomized to receive RT (external-beam RT plus brachytherapy) plus weekly CDDP chemotherapy (40 mg/m2) (arm 1) or the same RT without chemotherapy (arm 2).

RESULTS: A total of 253 patients were available for analysis. Median follow-up was 82 months. No significant difference was found in progression-free survival (P = .33). No significant difference in 3- and 5-year survival rates was found (69% v 66% and 62% v 58%, respectively; P = .42). The hazard ratio for survival (arm 2 to arm 1) was 1.10 (95% confidence interval, 0.75 to 1.62).

CONCLUSION: This study did not show a benefit to either pelvic control or survival by adding concurrent weekly CDDP chemotherapy in a dose of 40 mg/m2 to radical RT as given in this trial. Careful attention to RT details is important for achieving optimum outcome for patients with this disease.
Increased Cyclooxygenase-2 Expression Is Associated With Chemotherapy Resistance and Poor Survival in Cervical Cancer Patients
Authors: Ferrandina G. , Lauriola L. , Distefano M. G. , Zannoni G. F. , Gessi M. , Legge F. , Maggiano N. , Mancuso S. , Capelli A. , Scambia G. , Ranelletti F. O.
Published: February 2017

PURPOSE: To investigate the expression of cyclooxygenase (COX-2) and its association with clinicopathologic parameters and clinical outcome in patients with cervical cancer.

PATIENTS AND METHODS: The study included 84 patients with stage IB to IVA cervical cancer. Patients with early-stage cases (n = 21) underwent radical surgery, whereas patients with locally advanced cervical cancer (LACC) (n = 63) were first administered neoadjuvant cisplatin-based treatment and subjected to surgery in case of response. Immunohistochemical analysis was performed on paraffin-embedded sections with rabbit antiserum against COX-2.

RESULTS: COX-2–integrated density values in the overall population ranged from 1.2 to 82.3, with mean ± SE values of 27.4 ± 2.4. According to the chosen cutoff value, 36 (42.9%) of 84 patients were scored as COX-2 positive. COX-2 levels were shown to be highly associated with tumor susceptibility to neoadjuvant treatment. COX-2 showed a progressive increase from mean ± SE values of 19.9 ± 8.0 in complete responders through 31.5 ± 3.5 in partial responses to 44.8 ± 3.9 in patients who were not responsive (P = .0054). When logistic regression was applied, only advanced stage and COX-2 positivity retained independent roles in predicting a poor chance of response to treatment. COX-2–positive patients had a shorter overall survival (OS) rate than COX-2–negative patients. In patients with LACC, the 2-year OS rate was 38% in COX-2–positive versus 85% in COX-2–negative patients (P = .0001). In the multivariate analysis, only advanced stage and COX-2 positivity retained independent negative prognostic roles for OS.

CONCLUSION: The assessment of COX-2 status could provide additional information to identify patients with cervical cancer with a poor chance of response to neoadjuvant treatment and unfavorable prognosis.
INT 0123 (Radiation Therapy Oncology Group 94-05) Phase III Trial of Combined-Modality Therapy for Esophageal Cancer: High-Dose Versus Standard-Dose Radiation Therapy
Authors: Minsky Bruce D. , Pajak Thomas F. , Ginsberg Robert J. , Pisansky Thomas M. , Martenson James , Komaki Ritsuko , Okawara Gordon , Rosenthal Seth A. , Kelsen David P.
Published: February 2017

PURPOSE: To compare the local/regional control, survival, and toxicity of combined-modality therapy using high-dose (64.8 Gy) versus standard-dose (50.4 Gy) radiation therapy for the treatment of patients with esophageal cancer.

PATIENTS AND METHODS: A total of 236 patients with clinical stage T1 to T4, N0/1, M0 squamous cell carcinoma or adenocarcinoma selected for a nonsurgical approach, after stratification by weight loss, primary tumor size, and histology, were randomized to receive combined-modality therapy consisting of four monthly cycles of fluorouracil (5-FU) (1,000 mg/m2/24 hours for 4 days) and cisplatin (75 mg/m2 bolus day 1) with concurrent 64.8 Gy versus the same chemotherapy schedule but with concurrent 50.4 Gy. The trial was stopped after an interim analysis. The median follow-up was 16.4 months for all patients and 29.5 months for patients still alive.

RESULTS: For the 218 eligible patients, there was no significant difference in median survival (13.0 v 18.1 months), 2-year survival (31% v 40%), or local/regional failure and local/regional persistence of disease (56% v 52%) between the high-dose and standard-dose arms. Although 11 treatment-related deaths occurred in the high-dose arm compared with two in the standard-dose arm, seven of the 11 deaths occurred in patients who had received 50.4 Gy or less.

CONCLUSION: The higher radiation dose did not increase survival or local/regional control. Although there was a higher treatment-related mortality rate in the patients assigned to the high-dose radiation arm, it did not seem to be related to the higher radiation dose. The standard radiation dose for patients treated with concurrent 5-FU and cisplatin chemotherapy is 50.4 Gy.
Cardiac Dysfunction in the Trastuzumab Clinical Trials Experience
Authors: Seidman Andrew , Hudis Clifford , Pierri Mary Kathryn , Shak Steven , Paton Virginia , Ashby Mark , Murphy Maureen , Stewart Stanford J. , Keefe Deborah
Published: February 2017

PURPOSE: This study sought to estimate cardiac dysfunction (CD) risk for patients receiving trastuzumab; to characterize observed CD by severity, treatment, and clinical outcome; to assess effects of baseline clinical risk factors on CD; and to assess effects of cumulative doses of anthracyclines and trastuzumab on CD.

PATIENTS AND METHODS: A retrospective review of records for patients enrolled onto any of seven phase II and III trastuzumab clinical trials was performed. Predefined criteria were used for the diagnosis, and the New York Heart Association functional classification system was used to document CD severity. Product-limit estimates were used to summarize the cumulative anthracycline and trastuzumab doses at the time of CD onset.

RESULTS: Patients treated with trastuzumab were found to be at an increased risk for CD. The incidence was greatest in patients receiving concomitant trastuzumab and anthracycline plus cyclophosphamide (27%). The risk was substantially lower in patients receiving paclitaxel and trastuzumab (13%) or trastuzumab alone (3% to 7%); however, most of these patients had received prior anthracycline therapy. CD was noted in 8% of patients receiving anthracycline plus cyclophosphamide and 1% receiving paclitaxel alone. Most trastuzumab-treated patients developing CD were symptomatic (75%), and most improved with standard treatment for congestive heart failure (79%).

CONCLUSION: Trastuzumab is associated with an increased risk of CD, which is greatest in patients receiving concurrent anthracyclines. In most patients with metastatic breast cancer, the risk of CD can be justified given the improvement in overall survival previously reported with trastuzumab.
CD20 Expression in Hodgkin and Reed-Sternberg Cells of Classical Hodgkin’s Disease: Associations With Presenting Features and Clinical Outcome
Authors: Rassidakis George Z. , Medeiros L. Jeffrey , Viviani Simonetta , Bonfante Valeria , Nadali Gian-Paolo , Vassilakopoulos Theodoros P. , Mesina Ofelia , Herling Marco , Angelopoulou Maria K. , Giardini Roberto , Chilosi Marco , Kittas Christos , McLaughlin Peter , Rodriguez M. Alma , Romaguera Jorge , Bonadonna Gianni , Gianni Alessandro M. , Pizzolo Giovanni , Pangalis Gerassimos A. , Cabanillas Fernando , Sarris Andreas H.
Published: February 2017

PURPOSE: CD20 can be expressed in Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin’s disease (HD), but its clinical significance remains controversial. Therefore, we correlated CD20 expression with presenting features and clinical outcome of untreated patients with classical HD.

PATIENTS AND METHODS: Patients were eligible if they were previously untreated and human immunodeficiency virus-1 negative, had biopsy-proven classical HD, and if pretreatment paraffin-embedded tumor tissue was available. CD20 expression was determined by immunohistochemistry without knowledge of clinical outcome. A tumor was considered positive if any HRS cells expressed CD20, but other cutoffs for number of CD20-positive HRS were also investigated.

RESULTS: We identified 598 patients whose median age was 30 years and of whom 55% were male. HRS cells expressed CD20 in 132 (22%) of 598 patients with classical HD. When any percentage of CD20 expression in HRS cells was used as a cutoff, the 5-year failure-free survival (FFS) for positive versus negative tumors was 86% versus 84%, respectively, for 302 patients treated with doxorubicin, bleomycin, vinblastine, and dacarbazine or equivalent regimens (P = .7 by log-rank test), 74% versus 77%, respectively, for 181 patients treated with mitoxantrone, vincristine, vinblastine, and prednisone and radiotherapy (P = .7 by log-rank test), 74% versus 84%, respectively, for 54 patients treated with MOPP (P = .4 by log-rank test), and 77% versus 88% for 53 patients treated only with radiotherapy (P = .5 by log-rank test). The 5-year FFS was not statistically different when cutoffs of 5% up to 50% for CD20-positive HRS cells were used.

CONCLUSION: CD20 is expressed by HRS cells in 22% of patients with classical HD but is not associated with different FFS after treatment with equivalent regimens.
Rituximab and CHOP Induction Therapy for Newly Diagnosed Mantle-Cell Lymphoma: Molecular Complete Responses Are Not Predictive of Progression-Free Survival
Authors: Howard Orion M. , Gribben John G. , Neuberg Donna S. , Grossbard Michael , Poor Christina , Janicek Milos J. , Shipp Margaret A.
Published: February 2017

PURPOSE: To evaluate the efficacy of rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) induction therapy in patients with newly diagnosed mantle-cell lymphoma (MCL).

PATIENTS AND METHODS: From March 1997 to May 1999, 40 previously untreated patients with stage II through IV MCL were treated with six cycles of rituximab and CHOP chemotherapy in a phase II trial. Pretreatment and interval peripheral-blood (PB) and bone marrow (BM) specimens were also analyzed by polymerase chain reaction (PCR) for tumor-specific BCL-1/immunoglobulin H (IgH) translocations and clonal IgH rearrangements. Study end points included clinical and molecular response rates and long-term progression-free survival (PFS).

RESULTS: Forty-eight percent of patients achieved a complete response (CR)/CR unconfirmed (CRu), and 48% of patients obtained a partial response (PR). However, 28 of the 40 patients have already relapsed or developed progressive disease with a median PFS of 16.6 months. Twenty-five patients had PCR-detectable BCL-1/IgH or clonal IgH products in PB or BM at diagnosis. Nine of the 25 informative patients had no evidence of PCR-detectable disease in PB or BM after rituximab and CHOP therapy. However, patients who achieved molecular remissions in PB or BM had PFS similar to patients without molecular remissions (16.5 v 18.8 months, P = .51).

CONCLUSION: Favorable clinical and molecular response rates associated with rituximab and CHOP chemotherapy do not translate into prolonged PFS in MCL. Nevertheless, rituximab and combination chemotherapy may transiently clear PB or BM of detectable tumor cells, prompting additional consideration of antibody-based in vivo purging in subsequent clinical trials.
Combined-Modality Treatment for Resectable Metastatic Colorectal Carcinoma to the Liver: Surgical Resection of Hepatic Metastases in Combination With Continuous Infusion of Chemotherapy—An Intergroup Study
Authors: Kemeny M. Margaret , Adak Sudeshna , Gray Bruce , Macdonald John S. , Smith Thomas , Lipsitz Stuart , Sigurdson Elin R. , O’Dwyer Peter J. , Benson Al B.
Published: February 2017

PURPOSE: Despite technical improvements that have minimized the morbidity and mortality of hepatic surgery, the long-term outcome of resection of hepatic metastases of colorectal cancer remains poor, with the majority of patients experiencing treatment failure in the liver. Because arterial chemotherapy regimens targeted to the liver have demonstrated high response rates, an intergroup trial of adjuvant therapy for patients undergoing hepatic resection of liver metastases from colorectal cancer was initiated.

PATIENTS AND METHODS: Patients with one to three potentially resectable metastases were randomized preoperatively to receive no further therapy (control arm, 56 patients) or postoperative hepatic arterial floxuridine combined with intravenous continuous-infusion fluorouracil (chemotherapy arm, 53 patients). After exclusion of patients identified as ineligible for the planned treatment at the time of surgery, there were 45 control patients and 30 on the chemotherapy arm. The study was powered to evaluate improvement in time to recurrence and hepatic disease-free survival, not overall survival.

RESULTS: The 4-year recurrence-free rate was 25% for the control arm and 46% for the chemotherapy group (P = .04). The 4-year liver recurrence-free rate was 43% in the control group and 67% in the chemotherapy group (P = .03). The median survival of the 75 assessable patients was 49 months for the control arm and 63.7 months for the chemotherapy arm (P = .60). The median survival of all 109 patients was 47 months for the control arm compared with 34 months for the chemotherapy arm (P = .19)

CONCLUSION: These data demonstrate that adjuvant intra-arterial and intravenous chemotherapy was beneficial in prolonging time to recurrence and pre-venting hepatic recurrence after hepatic resection of colorectal cancer.
Volume of Lymphatic Metastases Does Not Independently Influence Prognosis in Colorectal Cancer
Authors: Wong Jan H. , Steinemann Susan , Tom Paul , Morita Shane , Tauchi-Nishi Pamela
Published: February 2017

PURPOSE: To evaluate the prognostic relevance of the volume of nodal metastatic disease in colorectal cancer patients.

PATIENTS AND METHODS: One hundred node-positive patients with T2 or T3 carcinoma of the colon or rectum after routine histologic examination of the regional nodes were studied. The metastatic tumor was measured with an ocular micrometer, and the tumor volume was determined.

RESULTS: The mean lymph node metastatic tumor volume was 5.1 ± 4.99 mm3 (range, 0.05 to 83,434 mm3). There was only a weak positive correlation with number of nodes involved with metastatic disease and tumor volume in nodes (r = .45). Median follow-up was 39 months (range, 1 to 87 months). The number of nodes was highly predictive of outcome. Individuals with one to three positive nodes had a substantially better survival than individuals with four or more positive nodes (P < .001). The volume of nodal metastatic disease correlated with outcome (P = .019). Patients dying as a result of disease had substantially greater mean metastatic nodal volume than those who were alive (3,705 v 1,783 mm3; P = .036). However, the total metastatic nodal volume did not, independent of positive nodes or number of positive nodes, predict outcome. Individuals with micrometastatic nodal volume did not have improved survival when compared with individuals with macrometastatic nodal volume (P = .79).

CONCLUSION: The number of nodes involved with metastatic tumor, rather the volume of metastatic involvement of the regional lymph nodes, predicts outcome. These results suggest that micrometastatic disease may have a similar prognosis as macrometastatic disease when the same number of lymph nodes are involved with metastatic tumor.
Gemcitabine Combined With Oxaliplatin in Advanced Pancreatic Adenocarcinoma: Final Results of a GERCOR Multicenter Phase II Study
Authors: Louvet C. , André T. , Lledo G. , Hammel P. , Bleiberg H. , Bouleuc C. , Gamelin E. , Flesch M. , Cvitkovic E. , de Gramont A.
Published: February 2017

PURPOSE: Based on preclinical in vitro synergy data, this study evaluated the activity and toxicity of a gemcitabine/oxaliplatin combination in patients with metastatic and locally advanced pancreatic adenocarcinoma.

PATIENTS AND METHODS: Previously untreated metastatic and locally advanced unresectable pancreatic adenocarcinoma patients were enrolled onto this multicenter phase II study. Patients received gemcitabine 1,000 mg/m2 as a 10-mg/m2/min infusion on day 1 and oxaliplatin 100 mg/m2 as a 2-hour infusion on day 2 every 2 weeks. Patients with metastatic disease were treated until evidence of progressive disease, whereas patients with locally advanced disease received six cycles in the absence of progression, followed when appropriate by concomitant radiochemotherapy.

RESULTS: Among 64 eligible patients included in eight centers, 30 had locally advanced and 34 had metastatic disease. Response rate for the 62 patients with measurable disease was 30.6% (95% confidence interval, 19.7% to 42.3%), 31.0% for locally advanced and 30.3% for metastatic patients. Among 58 assessable patients, 40% had clinical benefit. Median progression-free survival and median overall survival (OS) were 5.3 and 9.2 months, respectively, with 36% of patients alive at 1 year. Median OS for patients with metastatic disease and locally advanced disease were 8.7 and 11.5 months, respectively. With 574 treatment cycles (median per patient, nine; range, zero to 27), grade 3/4 toxicity per patient was 11% for neutropenia and thrombocytopenia, 14% for nausea or vomiting, 6.2% for diarrhea, and 11% for peripheral neuropathy, with no toxic deaths.

CONCLUSION: Palliative effects, response rate, and survival observed with this well-tolerated gemcitabine/oxaliplatin combination deserve additional evaluation. A comparative study of combination therapy versus gemcitabine alone is ongoing.
Randomized, Open-Label, Phase III Study of a 28-Day Oral Regimen of Eniluracil Plus Fluorouracil Versus Intravenous Fluorouracil Plus Leucovorin as First-Line Therapy in Patients With Metastatic/Advanced Colorectal Cancer
Authors: Schilsky Richard L. , Levin Jeremey , West William H. , Wong Alfred , Colwell Bruce , Thirlwell Michael P. , Ansari Rafat H. , Bell William N. , White Robin L. , Yates Barbara B. , McGuirt Paul V. , Pazdur Richard
Published: February 2017

PURPOSE: To compare the efficacy and tolerability of eniluracil (EU)/fluorouracil (5-FU) with that of 5-FU/leucovorin (LV) as first-line therapy for patients with metastatic/advanced colorectal cancer.

PATIENTS AND METHODS: This multicenter, randomized, open-label, phase III study (FUMA3008) conducted in the United States and Canada compared the safety and efficacy of EU/5-FU (11.5 mg/m2/1.15 mg/m2 twice daily for 28 days every 35 days) with that of intravenous 5-FU/LV (425 mg/m2/20 mg/m2 once daily for 5 days every 28 days) in patients with previously untreated metastatic colorectal cancer. Overall survival (OS) was the primary end point.

RESULTS: A total of 981 patients were randomized and 964 patients received treatment (485 EU/5FU, 479 5FU/LV). Survival for EU/5-FU was not statistically equivalent (but not statistically inferior) to that for 5-FU/LV (hazard ratio, 0.880; 95% confidence interval [CI], 0.75 to 1.03). Median duration of survival was 13.3 months in the EU/5-FU group and 14.5 months in the 5-FU/LV group. Median duration of progression-free survival for EU/5-FU was statistically inferior to that of the control group (20.0 weeks [95% CI, 19.1 to 20.9 weeks] v 22.7 weeks [95% CI, 18.3 to 24.6 weeks]; P = .01). Both treatments were well tolerated. Diarrhea was the most common nonhematologic toxicity in both groups; treatment-related grade 3 or 4 diarrhea occurred in 19% of patients treated with EU/5-FU and 16% of patients receiving 5-FU/LV (P = .354). Grade 3 or 4 granulocytopenia occurred in 5% of EU/5-FU patients and 47% of 5-FU/LV patients.

CONCLUSION: Safety profiles of both treatments were acceptable. Although antitumor activity was observed, EU/5-FU did not meet the protocol-specified statistical criteria for equivalence to 5-FU/LV in terms of OS.
Simplified Staging for Hepatocellular Carcinoma
Authors: Vauthey Jean-Nicolas , Lauwers Gregory Y. , Esnaola Nestor F. , Do Kim-Anh , Belghiti Jacques , Mirza Nadeem , Curley Steven A. , Ellis Lee M. , Regimbeau Jean-Marc , Rashid Asif , Cleary Karen R. , Nagorney David M.
Published: February 2017

PURPOSE: The current American Joint Committee on Cancer (AJCC) staging system for hepatocellular carcinoma (HCC) fails to stratify patients adequately with respect to prognosis.

PATIENTS AND METHODS: The ability of the currently proposed tumor (T) categories to effectively stratify the survival of 557 patients who underwent complete resection for HCC at four centers was examined. Independent predictors of survival were combined into a new staging system.

RESULTS: Using the current AJCC T classification, patients with T1 and T2 tumors had similar 5-year survivals (P = .6). In addition, the survival of patients with multiple bilobar tumors (T4) matched that of T3 patients (P = .5). Independent predictors of death were major vascular invasion (P < .001), microvascular invasion (P = .001), severe fibrosis/cirrhosis of the host liver (P = .001), multiple tumors (P = .007), and tumor size greater than 5 cm (P = .01). Based on our results, a simplified stratification is proposed: (a) patients with a single tumor and no microvascular invasion, (b) patients with a single tumor and microvascular invasion or multiple tumors, none more than 5 cm, and (c) patients with either multiple tumors, any more than 5 cm, or tumor with major vascular invasion (P < .001). Severe fibrosis/cirrhosis had a negative impact on survival within all categories. The survival of patients with lymph node involvement matched that of patients with major vascular invasion (P = .3).

CONCLUSION: The current AJCC staging system for HCC is unnecessarily complex. We propose a simplified model of stratification that is based on vascular invasion, tumor number, and tumor size and incorporates the effect of fibrosis on survival.
Cancer Incidence in a Population of Jewish Women at Risk of Ovarian Cancer
Authors: Liede Alexander , Karlan Beth Y. , Baldwin Rae Lynn , Platt Lawrence D. , Kuperstein Graciela , Narod Steven A.
Published: February 2017

PURPOSE: To evaluate the incidence and clinical characteristics of ovarian and other cancers in a cohort of women at risk of developing ovarian cancer.

PATIENTS AND METHODS: The Gilda Radner Ovarian Cancer Detection Program in Los Angeles, CA, was established in 1991 to study the efficacy of screening in the early detection of ovarian cancer. We present findings from a historical cohort of 290 Jewish women who were offered BRCA testing for three common founder mutations (BRCA1 185delAG and 5382insC and BRCA2 6174delT).

RESULTS: In 10 years, 17 cancers were observed (1,111 per 100,000 per year), including six breast and eight ovarian or related cancers. A high proportion of cancers of peritoneal origin was observed. The majority (86%) of women with incident breast or ovarian/peritoneal cancer carried a mutation in the BRCA1 gene. The overall cancer incidence among carriers of mutations in the BRCA1 gene was estimated to be 5,450 per 100,000 per year, corresponding to a cumulative incidence of 47.5% at 10 years. In contrast, the cumulative incidence of cancer among noncarriers was 2.5% (P < 10−8). After adjustment for sampling, the risks to BRCA1 mutation carriers at 10 years were estimated to be 21% for ovarian/peritoneal/tubal cancer, 16% for breast cancer, and 36% for all cancers.

CONCLUSION: The excess risk of breast and ovarian cancer in Jewish women with a family history of ovarian cancer is largely attributable to mutations in BRCA1. Intensive surveillance by use of CA-125 and ultrasound does not seem to be an effective means of diagnosing early-stage ovarian cancer in this high-risk cohort.
Phase II Trial of Docetaxel and Cisplatin Combination Chemotherapy in Patients With Squamous Cell Carcinoma of the Head and Neck
Authors: Glisson Bonnie S. , Murphy Barbara A. , Frenette Gary , Khuri Fadlo R. , Forastiere Arlene A.
Published: February 2017

PURPOSE: To assess the antitumor activity and toxicity of docetaxel plus cisplatin chemotherapy in patients with recurrent or incurable squamous cell carcinoma of the head and neck (SCCHN).

PATIENTS AND METHODS: Patients with recurrent or incurable SCCHN were eligible if they were chemotherapy naive or if they had received one prior regimen as neoadjuvant or concurrent treatment with radiation. Patients who had received chemotherapy for recurrence or prior taxanes were ineligible. Patients received docetaxel 75 mg/m2 and cisplatin 75 mg/m2 on day 1; cycles were repeated every 21 days.

RESULTS: Toxic effects and length of survival were assessable in 36 patients and tumor response was assessable in 32, for whom the overall response rate was 40% (13 of 32) (6% complete response and 34% partial response). Median time to response was 5 weeks, and median duration was 4.9 months. In the intent to treat population (n = 36), median time to disease progression was 4 months. Median survival (n = 36) was 9.6 months, and the 12-month survival rate was 27%. Grade 4 neutropenia was observed in 71% of patients. Two patients (6%) experienced serious fever during grade 4 neutropenia (without documented infection) that required intravenous antibiotics, and an additional four patients had grade 3 infection. Other severe (grades 3 and 4) toxic effects were asthenia (25%), nausea (11%), fever (8%), vomiting (8%), severe hypersensitivity reactions (8%), and diarrhea (8%). Severe stomatitis (grade 3) occurred in only one patient.

CONCLUSION: Docetaxel plus cisplatin is an effective regimen with an acceptable safety profile for palliation of recurrent SCCHN. Relative to the standard regimen of cisplatin/fluorouracil, this regimen may offer higher tumor response and survival rates with short outpatient administration and a lower incidence of severe mucosal toxicity.
Cisplatin, Dacarbazine With or Without Subcutaneous Interleukin-2, and Interferon Alfa-2b in Advanced Melanoma Outpatients: Results From an Italian Multicenter Phase III Randomized Clinical Trial
Authors: Ridolfi Ruggero , Chiarion-Sileni Vanna , Guida Michele , Romanini Antonella , Labianca Roberto , Freschi Andrea , Lo Re Giovanni , Nortilli Rolando , Brugnara Sonia , Vitali Patrizia , Nanni Oriana
Published: February 2017

PURPOSE: Phase II and III studies have shown that the addition of interleukin-2 (IL-2) and interferon alfa-2b (IFNα-2b) in multiagent chemotherapy (CT) for advanced melanoma increases overall response (OR), albeit without clear evidence of an improvement in overall survival (OS). Treatment with high-dose IL-2 can cause severe toxicity and is normally administered in an inpatient setting. We conducted a multicenter prospective randomized clinical trial in outpatients with metastatic melanoma to compare CT with biochemotherapy (bioCT) using immunomodulant doses of IL-2 and IFNα-2b.

PATIENTS AND METHODS: One hundred seventy-six eligible patients with advanced melanoma were randomized to receive CT (cisplatin and dacarbazine with or without carmustine every 21 days) or bioCT comprising the same CT regimen followed by low-dose subcutaneous IL-2 for 8 days and IFNα2b three times a week, both for six cycles.

RESULTS: At a median follow-up of 18 (CT) and 16 (bioCT) months, median OS was 9.5 versus 11.0 months (P = .51), respectively. In the 89 CT-arm patients, 18 ORs (20.2%) (three complete responders [CRs] and 15 partial responders [PRs]) were observed according to World Health Organization criteria. In the 87 bioCT-arm patients, 22 ORs (25.3%) (three CRs and 19 PRs) (P = .70) were recorded. Treatment-related toxicity was fairly similar in both arms.

CONCLUSION: The addition of low-dose immunotherapy did not produce a statistically significant advantage in OS, time to progression, or OR. However, the 11-month median OS in the bioCT arm does not differ greatly from the best results with high-dose IL-2–containing regimens reported in the literature. Furthermore, our treatment schedule was carried out on outpatients and had an acceptable level of toxicity.