Deoxycitidine kinase is associated with prolonged survival after adjuvant gemcitabine for resected pancreatic adenocarcinoma.
; ; et al
in Cancer (2010), 116(22), 5200-6
BACKGROUND: Gemcitabine (2',2'-difluorodeoxycytidine) administration after resection of pancreatic cancer improves both disease-free survival (DFS) and overall survival (OS). Deoxycytidine kinase (dCK ... [more ▼]
BACKGROUND: Gemcitabine (2',2'-difluorodeoxycytidine) administration after resection of pancreatic cancer improves both disease-free survival (DFS) and overall survival (OS). Deoxycytidine kinase (dCK) mediates the rate-limiting catabolic step in the activation of gemcitabine. The authors of this report studied patient outcomes according to the expression of dCK after a postoperative gemcitabine-based chemoradiation regimen. METHODS: Forty-five patients with resected pancreatic adenocarcinoma received adjuvant gemcitabine based-therapy in the context of multicenter phase 2 studies. Their tumors were evaluated retrospectively for dCK protein expression by immunohistochemistry. A composite score based on the percentage of dCK-positive cancer cells and the intensity of staining was generated, and the results were dichotomized at the median values. RESULTS: The median follow-up was 19.95 months (95% confident interval [CI], 3.3-107.4 months). The lymph node (LN) ratio and dCK protein expression were significant predictors of DFS and OS in univariate analysis. On multivariate analysis, dCK protein expression was the only independent prognostic variable (DFS: hazard ratio [HR], 3.48; 95% CI, 1.66-7.31; P = .001; OS: HR, 3.2; 95% CI,1.44-7.13; P = .004). CONCLUSIONS: dCK protein expression was identified as an independent and strong prognostic factor in patients with resected pancreatic adenocarcinoma who received adjuvant gemcitabine therapy. The authors concluded that it deserves prospective evaluation as a predictive biomarker for patient selection. [less ▲]Detailed reference viewed: 14 (2 ULg)
Factors that influence physicians' detection of distress in patients with cancer - Can a communication skills training program improve physicians' detection?
; ; et al
in Cancer (2005), 104(2), 411-421
BACKGROUND. No study to date has assessed the impact of skills acquisition after a communication skills training program on physicians' ability to detect distress in patients with cancer. METHODS. First ... [more ▼]
BACKGROUND. No study to date has assessed the impact of skills acquisition after a communication skills training program on physicians' ability to detect distress in patients with cancer. METHODS. First, the authors used a randomized design to assess the impact, on physicians' ability to detect patients' distress, of a 1-hour theoretical information course followed by 2 communication skills training programs: a 2.5-day basic training program and the same training program consolidated by 6 3-hour consolidation workshops. Then, the investigate contextual, patient, and communication variables or factors associated with physicians' detection of patients' distress were investigated. After they attended the basic communication skills training program, physicians were assigned randomly to consolidation workshops or to a waiting list. Interviews with a cancer patient were recorded before training, after consolidation workshops for the group that attended consolidation workshops, and approximate to 5 months after basic training for the group that attended basic training without the consolidation workshops. Patient distress was recorded with the Hospital Anxiety and Depression Scale before the interviews. Physicians rated their patients' distress on a visual analog scale after the interviews. Physicians' ability to detect patients' distress was measured through computing differences between physicians' ratings of patients' distress and patients' self-reported distress. Communication skills were analyzed according to the Cancer Research Campaign Workshop Evaluation Manual. RESULTS. Fifty-eight physicians were evaluable. Repeated -measures analysis of variance showed no statistically significant changes over time and between groups in physicians' ability to assess patient distress. Mixed-effects modeling showed that physicians' detection of patients' distress was associated negatively with patients' educational level (P = 0.042) and with patients' self-reported distress (P < 0.000). Mixed-effects modeling also showed that physicians' detection of patient distress was associated positively with physicians breaking bad news (P = 0.022) and using assessment skills (P = 0.015) and supportive skills (P = 0.045). CONCLUSIONS. Contrary to what was expected, no change was observed in physicians' ability to detect distress in patients with cancer after a communication skills training programs, regardless of whether physicians attended the basic training program or the basic training program followed by the consolidation workshops. The results indicated a need for further improvements in physicians' detection skills through specific training modules, including theoretical information about factors that interfere with physicians' detection and through role-playing exercises that focus on assessment and supportive skills that facilitate detection. (c) 2005 American Cancer Society. [less ▲]Detailed reference viewed: 30 (0 ULg)
Age-related performance of human papillomavirus testing used as an adjunct to cytology for cervical carcinoma screening in a population with a low incidence of cervical carcinoma
; ; Goffin, Frédéric et al
in Cancer (2005), 105(3), 126-132
BACKGROUND. High-risk human papillomavirus (HR-HPV) testing has been proposed as a replacement for cytology or as an adjunct to cytology for primary cervical carcinoma screening. The objective of this ... [more ▼]
BACKGROUND. High-risk human papillomavirus (HR-HPV) testing has been proposed as a replacement for cytology or as an adjunct to cytology for primary cervical carcinoma screening. The objective of this study was to assess the age-specific prevalence of HR-HPV infection and the correlation between HR-HPV status and cytologic diagnosis. METHODS. The authors enrolled 7254 women receiving routine cytologic screening in a cross-sectional study that was conducted during 12 months. Cervical samples were collected using liquid-based cytology to perform both Papanicolaou smears and HR-HPV testing. Analyses were performed using age stratification, and the cytologic results were considered as the reference diagnosis for parameter analysis tests. RESULTS. The overall rate of HR-HPV infection was 11.4% (95% confidence interval, 9-12%) and was higher in younger women compared with older women (age < 30 years vs. >= 30 years; 16% vs. 8.5%, respectively; P < 0.0001). The overall rate of abnormal cytology was 3.2% and, similarly, was more prevalent in younger women (6.1% vs. 2.4%; P < 0.0001). The best balance between sensitivity and specificity for high-grade lesions or worse occurred predominantly in older age groups (age >= 50 years). CONCLUSIONS. The prevalence of HR-HPV was age-dependent, with the strongest correlation between HR-HPV positivity and disease observed among older women, who potentially may derive the most benefit. (c) 2005 American Cancer Society. [less ▲]Detailed reference viewed: 14 (1 ULg)
Physicians' communication with a cancer patient and a relative - A randomized study assessing the efficacy of consolidation workshops
; ; et al
in Cancer (2005), 103(11), 2397-2411
BACKGROUND. Although patients with cancer are often accompanied by a relative during medical interviews, to the authors' knowledge little is known regarding the efficacy of communication skills training ... [more ▼]
BACKGROUND. Although patients with cancer are often accompanied by a relative during medical interviews, to the authors' knowledge little is known regarding the efficacy of communication skills training programs on physicians' communication skills in this context. The objective of the current study was to assess the efficacy of 6 consolidation workshops, 3 hours in length, that were conducted after a 2.5-day basic training program. METHODS. After attending the basic training program, physicians were assigned randomly to consolidation workshops or to a waiting list. Training efficacy was assessed through simulated and actual interviews that were recorded on an audio tape at baseline, after consolidation workshops for the consolidation-workshops group, and 5 months after the end of basic training for the waiting-list group. Communication skills were assessed according to the Cancer Research Campaign Workshop Evaluation Manual. Patients' and relatives' perceptions of and satisfaction with physicians' communication performance were assessed using a 15-item questionnaire. RESULTS. Sixty-two physicians completed the training program. Compared with physicians who participated to the basic training program, when addressing the patient, physicians who were randomized to the consolidation workshops used more open, open directive, and screening questions (P = 0.011 in simulated patient interviews and P = 0.005 in actual patient interviews) and elicited and clarified psychologic concerns more often (P = 0.006 in simulated patient interviews and P < 0.001 in actual patient interviews). When they addressed the relative, physicians who were randomized to the consolidation workshops gave less premature information (P = 0.032 in simulated patient interviews and P < 0.001 in actual patient interviews). When they addressed the patient and the relative simultaneously, physicians who were randomized to the consolidation workshops used more empathy, educated guesses, alerting to reality, confronting, negotiating, and summarizing (P = 0.003 in simulated patient interviews and P = 0.024 in actual patient interviews). Patients, but not relatives, who interacted with physicians in the consolidation-workshops group were more satisfied globally with the interviews (P = 0.022). CONCLUSIONS. Six 3-hour consolidation workshops resulted in improved communication skills addressed to patients and to relatives. The current results showed that the transfer of skills addressing relatives' concerns remained limited and that consolidation workshops should focus even more systematically on the practice of three-person interviews. (c) 2005 American Cancer Society. [less ▲]Detailed reference viewed: 16 (2 ULg)
Importance of Tumor Regression Assessment in Predicting the Outcome in Patients with Locally Advanced Rectal Carcinoma Who Are Treated with Preoperative Radiotherapy
; ; et al
in Cancer (2002), 94(4), 1121-1130
BACKGROUND: Locally advanced rectal carcinoma has a poor prognosis. However, <br />since the introduction of preoperative radiotherapy, the outcome of patients with <br />rectal carcinoma has been ... [more ▼]
BACKGROUND: Locally advanced rectal carcinoma has a poor prognosis. However, <br />since the introduction of preoperative radiotherapy, the outcome of patients with <br />rectal carcinoma has been reported to have improved. Nevertheless, to the authors’ <br />knowledge few data are available regarding the histopathologic response to <br />radiotherapy as assessed on surgical specimens as a potential predictive factor for <br />outcome. <br />METHODS: To estimate the effect of radiotherapy on rectal carcinoma, the authors <br />retrospectively reviewed the surgical specimens of 102 patients with T3-4, N0 or <br /> N1 rectal carcinoma and 1 patient with T2 but N1 rectal carcinoma. All patients <br />were treated preoperatively with a hyperfractionated accelerated radiotherapy <br />schedule in a prospective protocol (Trial 93-01). Using a standardized approach, <br />tumor regression was graded using a system that varies from Grade 1 (tumor <br />regression Grade [TRG] 1) when complete tumor regression is observed to Grade 5 <br />(TRG5) when no tumor regression is observed. <br />RESULTS: Radiotherapy resulted in tumor downstaging in 43% of the patients. <br />There were 2 pT1 tumors (2%), 21 pT2 tumors (20%), 66 pT3 tumors (64%), and 14 <br />pT4 tumors (14%) after treatment. Regional lymph nodes were involved in 55 <br />patients (53%). None of the patients demonstrated a complete tumor regression <br />after radiotherapy, but in 79% of the specimens a partial tumor regression was <br />observed (TRG1: 0%; TRG2: 20%; TRG3: 39%; TRG4: 20%; and TRG5: 21%). The <br />median actuarial overall survival (OS) and disease-free survival (DFS) were 52 <br />months. Actuarial local recurrence rates at 2 years and 5 years were 6.4% and 7.6%, <br />respectively. Univariate analysis showed the actuarial DFS to be significantly lower <br />in patients with lymph node metastases (P 0.0004) and advanced pT stages <br />(pT3-4) (P 0.03). A favorable outcome for OS, DFS, and local control was <br />observed in patients with TRG2-4 (i.e., responders) compared with patients with <br />TRG5 (i.e., nonresponders), but also in patients with low residual tumor cell <br />density (TRG2, 3, and 4). On multivariate analysis, TRG remained an independent <br />prognostic indicator for local tumor control. <br />CONCLUSIONS. Tumor regression as well as residual tumor cell density were found <br />to be predictive factors of survival in rectal carcinoma patients after preoperative <br />radiotherapy. Even after preoperative radiotherapy, the pathologic stage of the <br />surgical specimen remained a prognostic factor. The use of a standardized approach <br />for pathologic evaluation must be implemented to allow comparison between <br />the results of various treatment approaches. [less ▲]Detailed reference viewed: 23 (2 ULg)
Role of methalothionein in irradiated human rectal carcinoma.
; ; et al
in Cancer (2002), 95(5), 1003-1008
BACKGROUND. Metallothioneins (MT) are low-molecular weight, metal-binding proteins that play a role in cellular proliferation and differentiation, as well as in cellular defense mechanisms. They act as ... [more ▼]
BACKGROUND. Metallothioneins (MT) are low-molecular weight, metal-binding proteins that play a role in cellular proliferation and differentiation, as well as in cellular defense mechanisms. They act as scavengers of free radicals produced by irradiation. A number of in vitro and in vivo studies have linked overexpression of cellular MT with tumor cell resistance to radiation. This is the first study that investigates whether MT expression is involved in the radioresistance of rectal carcinoma. METHODS. Using a mouse monoclonal antibody, MT expression was analyzed by immunohistochemistry on surgical samples (n 85) from 85 patients with locally advanced rectal carcinoma who were treated preoperatively with a hyperfractionated and accelerated radiotherapy schedule and on tumor biopsies (n 13) obtained before treatment. The potential correlations between MT expression and pathologic variables and survival were examined. RESULTS. MT were expressed strongly in both the cytoplasm and nucleus of tumor cells in 7 biopsy and 42 surgical samples. A comparison of MT expression in biopsy and surgical specimens showed that MT expression did not change after irradiation in most cases. Against all expectations, MT were expressed more frequently in tumors from responders than in those from the nonresponders (P 0.02). There was no correlation between MT expression and tumor stage, histology after radiotherapy, or survival. CONCLUSION. These findings do not support the hypothesis that MT overexpression at the end of radiotherapy is a marker for radiation resistance. Cancer 2002;95: 1003–8. © 2002 American Cancer Society. DOI 10.1002/cncr.10780 [less ▲]Detailed reference viewed: 28 (0 ULg)
Adjuvant small field pelvic radiation for patients with high risk, stage IB lymph node negative cervix carcinoma after radical hysterectomy and pelvic lymph node dissection. A pilot study.
KRIDELKA, Frédéric ; ; et al
in Cancer (1999), 86(10), 2059-65
BACKGROUND: After radical hysterectomy and pelvic lymph node dissection, an identifiable subgroup of patients with International Federation of Gynecology and Obstetrics Stage IB lymph node negative cervix ... [more ▼]
BACKGROUND: After radical hysterectomy and pelvic lymph node dissection, an identifiable subgroup of patients with International Federation of Gynecology and Obstetrics Stage IB lymph node negative cervix carcinoma remains at high risk of pelvic recurrence. This study attempted to determine whether postoperative small field of pelvic radiation can improve the disease free survival (DFS) of this high risk group of patients without producing significant morbidity. METHODS: Between 1991 and 1995, after radical surgery, 25 patients with Stage IB lymph node negative cervix carcinoma were considered to be at high risk of pelvic recurrence on the basis of tumor dimension, depth of stromal invasion, and the presence of lymph-vascular space invasion. All had a score >/= 120 as determined by the Gynecologic Oncology Group (GOG) study. These patients received 50.4 gray of adjuvant radiation to a small central pelvic field and were followed prospectively. A Kaplan-Meier 5-year DFS curve was generated. A log rank analysis produced an estimated log rank P value (est P value) by comparing the 5-year DFS of the patients in the current study with the 5-year DFS of the corresponding high risk group of the GOG study (observation only). The morbidity of small field pelvic radiation was recorded. RESULTS: Among the 25 patients who received small field pelvic radiation, the mean GOG score was 166 (range, 120-263) and the mean follow-up was 32 months (range, 12-64 months). There was 1 recurrence (4%) recorded at 16 months. The log rank analysis demonstrated a significant improvement in the 5-year DFS for the group who received adjuvant small field pelvic radiation (est P value = 0.005) when compared with the DFS of the high risk GOG patients who were observed postoperatively. Four cases of minor morbidity were recorded: lymphedema (three cases) and mild rectal incontinence (one case). No major morbidity was reported. CONCLUSIONS: With low morbidity, adjuvant small field pelvic radiation appears to improve significantly the 5-year DFS of patients with high risk, lymph node negative Stage IB cervical carcinoma. However, this pilot study requires verification. [less ▲]Detailed reference viewed: 31 (0 ULg)
Long term follow-up of patients with acute myelogenous leukemia who received the daunorubicin, vincristine, and cytosine arabinoside regimen.
Beguin, Yves ; Sautois, Brieuc ; Forget, Patricia et al
in Cancer (1997), 79(7), 1351-4
BACKGROUND: In 1985, the authors published a study of acute myelogenous leukemia (AML) patients treated with a chemotherapeutic regimen that was then considered intensive. Ten years later, the authors ... [more ▼]
BACKGROUND: In 1985, the authors published a study of acute myelogenous leukemia (AML) patients treated with a chemotherapeutic regimen that was then considered intensive. Ten years later, the authors reanalyzed the same cohort to determine whether the very promising actuarial results observed at 5 years held after longer follow-up. METHODS: Between 1977 and 1982, 61 patients with AML were treated with a protocol consisting of daunorubicin, vincristine, and cytosine arabinoside induction followed by consolidation and maintenance for a total of 2 years. The complete remission (CR) rate was 66%, 84% in males versus 47% in females (P < 0.005). At the time of the first analysis in 1984, the overall survival (OS) was 17%, the projected 5-year continuous CR rate (CCR) 32%, and the disease free survival (DFS) rate 29%, with the best results observed for males and for patients ages 40-60 years (P < 0.05). RESULTS: When the data were reanalyzed 11 years later in 1995, the results were 14% OS, 23% CCR, and 16% DFS at 5 years. However, these figures dropped to 8%, 18%, and 11% at 10 years and to 8%, 12%, and 7% at 15 years, respectively. Among the 40 CR patients, 31 relapsed (up to 13 years after CR), and all died within 1.6 years after relapse. Nine patients were in CCR: 4 died of unrelated causes (suicide, alcoholic cirrhosis, acute peritonitis, or bladder carcinoma), 1 was lost to follow-up after 11 years, 2 were alive and well at 17 years at last follow-up, and 2 were transplanted in first CR and were doing well at 13 and 14 years at last follow-up. The survival advantage for males over females persisted (P = 0.0197), but the advantage for patients age 40-60 years did not hold. CONCLUSIONS: These long term data indicate that actuarial analysis at 5 years may overestimate the cure rate of AML patients because a number of late relapses do occur. However, the picture is blurred by the incidence of death not related to leukemia or its treatment; and when these patients were censored at the time of death, 17% of CR patients were still projected to be alive and free of leukemia after 17 years. [less ▲]Detailed reference viewed: 22 (6 ULg)
Postoperative Radiation Therapy for Rectal Cancer: An Interim Analysis of a Prospective, Randomized Multicenter Trial in The Netherlands
in Cancer (1992), 68(12), 3016-3019Detailed reference viewed: 9 (0 ULg)
Observations of serum trace elements in chronic lymphocytic leukemia.
Beguin, Yves ; Brasseur, Françoise ; Weber, Géraldine et al
in Cancer (1987), 60(8), 1842-6
Serum trace elements (STE) were measured in 50 patients with chronic lymphocytic leukemia (CLL) and 100 normal subjects. Copper was higher in patients than in controls (1.50 +/- 0.06 versus 1.10 +/- 0.02 ... [more ▼]
Serum trace elements (STE) were measured in 50 patients with chronic lymphocytic leukemia (CLL) and 100 normal subjects. Copper was higher in patients than in controls (1.50 +/- 0.06 versus 1.10 +/- 0.02 micrograms/ml, P less than 0.001), increased steadily from Stage 0 to Stage 4 (P = 0.002), and correlated with the lymphocyte count and serum lactate dehydrogenase (P less than 0.01) but not with acute phase reactants. Zinc was lower in patients than in controls (0.94 +/- 0.03 versus 1.10 +/- 0.02 micrograms/ml, P less than 0.001). Zinc (NS), selenium (P = 0.039), and calcium (P = 0.033), were decreased in Stages 3-4 as compared to Stages 0-2. The copper-to-zinc ratio (CZR) increased continuously from Stage 0 to Stage 4 (P less than 0.001). Discriminant analysis between two groups, Stage 0-2 and Stage 3-4, based on serum copper, zinc, calcium, and protein levels, allowed for a correct classification of 94% of the patients. Moreover, the clinical staging of the remaining 6% was modified retrospectively according to the results of discriminant analysis. It was concluded that (1) serum copper and CZR are useful indices of the extent of disease, (2) they are independent of a nonspecific acute phase reaction, (3) STE determination could be helpful in the staging of a limited number of CLL patients, and (4) zinc deficiency could contribute to immune dysfunction in CLL. [less ▲]Detailed reference viewed: 33 (5 ULg)
Treatment of acute nonlymphocytic leukemia in young and elderly patients.
Beguin, Yves ; ; Fillet, Georges et al
in Cancer (1985), 56(11), 2587-92
Among 95 consecutive patients with acute nonlymphocytic leukemia (ANLL), 61 were treated with a high-dose chemotherapeutic induction regimen consisting of daunorubicin, vincristine, and cytosine ... [more ▼]
Among 95 consecutive patients with acute nonlymphocytic leukemia (ANLL), 61 were treated with a high-dose chemotherapeutic induction regimen consisting of daunorubicin, vincristine, and cytosine arabinoside (DOA). The complete remission (CR) rate was 66%. Although young patients responded better than older patients, only sex was found to be of prognostic significance for achieving CR (84% CR in men versus 47% in women, P less than 0.005, independent of age). Patients in CR received consolidation, monthly maintenance therapy, and late intensification for a period of 2 years. Median remission duration was 57 weeks and median survival, 93 weeks. Projected CR rate at 5 years was 30%. CR and survival duration were significantly longer in patients 40 to 60 years old when compared with younger and older patients (P = 0.023). They were also longer in male than in female patients (P = 0.018), but this may be due to an effect of age. In the 34 patients who did not receive DOA treatment because of age or poor clinical conditions, there was no survival beyond 57 weeks, except in a 73-year-old woman who reached a spontaneous remission during acute infection. ANLL characteristics at presentation revealed a tendency toward a smaller tumor mass (P less than 0.05) and rarer Auer rods present (P = 0.03) with increasing age. Features and treatment of ANLL in elderly patients are discussed in view of the poor results obtained with conservative management. [less ▲]Detailed reference viewed: 25 (4 ULg)