Estimating the need for radiotherapy for lung cancer: an evidence-based, epidemiologic approach

BACKGROUND AND OBJECTIVES: Current estimates of the proportion of cancer patients who will require radiotherapy (RT) are based almost entirely on expert opinion. The objective of this study was to use an evidence-based approach to estimate the proportion of incident cases of lung cancer that will require RT at any point in the evolution of the illness. METHODS: A systematic review of the literature was undertaken to identify indications for RT for lung cancer, and to ascertain the level of evidence that supported each indication. An epidemiologic approach was then used to estimate the incidence of each indication for RT in a typical North American population of lung cancer patients. The effect of sampling error on the estimated appropriate rate of RT was calculated mathematically, and the effect of systematic error, was estimated by sensitivity analysis. RESULTS: It was shown that 53.6% +/- 3.3% of small-cell lung cancer (SCLC) cases develop one or more indications for RT at some point in the course of the illness, 45.4% +/- 4.3% in their initial treatment, and 8.2% +/- 1.5% later for recurrence of progression. Overall, 64.3% +/- 4.7% of non-small-cell lung cancer (NSCLC) cases require RT, 45.9% +/- 4.3% in their initial treatment, and 18.3% +/- 1.8% later in the course of the illness. The proportion of NSCLC cases that ever require RT is stage dependent; 41.0% +/- 5.5% in Stage I; 54.5% +/- 6.5% in Stage II; 83.5% +/- 10.6% in Stage III; and 65.7% +/- 7.6% in Stage IV. In total, 61.0% +/- 3.9% of all patients with lung cancer will develop one or more indications for RT at some point in the illness, 44.6% +/- 3.6% in their initial treatment, and 16.5% +/- 1.5% later for recurrence or progression. CONCLUSION: This method provides a rational starting point for the long-term planning of radiation services, and for the audit of access to RT at the population level. We now plan to extend this study to the other major cancer sites to enable us to estimate the appropriate RT treatment rate for the cancer population as a whole.     

Evidence-based estimate of appropriate radiotherapy utilization rate for prostate cancer

PURPOSE: Current estimates of the proportion of cancer patients who will require radiotherapy (RT) are based almost entirely on expert opinion. The objective of this study was to use an evidence-based approach to estimate the proportion of incident cases of prostate cancer that should receive RT at any point in the evolution of the illness. METHODS AND MATERIALS: A systematic review of the literature was undertaken to identify indications for RT for prostate cancer and to ascertain the level of evidence that supported each indication. An epidemiologic approach was then used to estimate the incidence of each indication for RT in a typical North American population of prostate cancer patients. The effect of sampling error on the estimated appropriate rate of RT was calculated mathematically, and the effect of systematic error using alternative sources of information was estimated by sensitivity analysis. RESULTS: It was estimated that 61.2% +/- 5.6% of prostate cancer cases develop one or more indications for RT at some point in the course of the illness. The plausible range for this rate was 57.3%-69.8% on sensitivity analysis. Of all prostate cancer patients, 32.2% +/- 3.8% should receive RT in their initial treatment and 29.0% +/- 4.1% later for recurrence or progression. The proportion of cases that ever require RT is risk grouping dependent; 43.9% +/- 2.2% in low-risk disease, 68.7% +/- 3.5% in intermediate-risk disease; and 79.0% +/- 3.8% in high-risk locoregional disease. For metastatic disease, the predicted rate was 66.4% +/- 0.3%. CONCLUSION: This method provides a rational starting point for the long-term planning of radiation services and for the audit of access to RT at the population level. By completing such evaluations in major cancer sites, it will be possible to estimate the appropriate RT rate for the cancer population as a whole.     

An evidence-based estimate of appropriate radiotherapy utilization rate for breast cancer

Current estimates of the proportion of cancer patients who will require radiotherapy (RT) are based almost entirely on expert opinion. We sought to use an evidence-based approach to estimate the proportion of incident cases of breast cancer that will require RT at any point in the evolution of the illness.

We undertook a systematic review of the literature to identify indications for RT for breast cancer and to ascertain the level of evidence that supported each indication. An epidemiologic approach was then used to estimate the incidence of each indication for RT in a typical North American population of breast cancer patients. The effect of sampling error on the estimated appropriate rate of RT was calculated mathematically, and the effect of systematic error was estimated by sensitivity analysis.

It was estimated that 66.4% ± 4.8% of breast cancer patients develop one or more indications for RT at some point in the course of the illness. The plausible range for this rate was 56.3%–72.4% on sensitivity analysis. Of all breast cancer patients, 57.3% ± 4.7% require RT in their initial treatment and 9.1% ± 1.0% do so later for recurrence or progression. The proportion of patients who ever require RT is stage dependent: 39.8% ± 1.1% in ductal carcinoma in situ; 68.6% ± 4.1% in Stage I invasive carcinoma; 81.5% ± 2.3% in Stage II; 95.3% ± 0.3% in Stage III; and 63.7% ± 0.3% in Stage IV.

This method provides a rational starting point for the long-term planning of RT services and for the audit of access to RT at the population level. By completing such evaluations in the major cancer sites, it will be possible to estimate the appropriate RT treatment rate for the cancer population as a whole.     

An evidence-based estimate of the appropriate rate of utilization of radiotherapy for cancer of the cervix

PURPOSE: Current estimates of the proportion of cancer patients who will require radiotherapy (RT) are based almost entirely on expert opinion. The objective of this study was to calculate the proportion of incident cases of cervical cancer that should receive RT by application of an evidence-based approach. METHODS AND MATERIALS: A systematic review of the literature was done to identify indications for RT for cervical cancer and to ascertain the level of evidence that supported each indication. A survey of Canadian gynecologic oncologists and radiation oncologists who treat cervical cancer was done to determine the level of acceptance of each indication among doctors who practice in the field. An epidemiologic approach was then used to estimate the incidence of each indication for RT in a typical North American population of patients with cervical cancer. RESULTS: The systematic review of the literature identified 29 different indications for RT for cervical cancer. The majority of the 75 experts who responded to the mail survey stated that they "usually" or "always" recommended RT in all but one of the clinical situations that were identified as indications for RT on the basis of the systematic review. The analysis of epidemiologic data revealed that, in a typical North American population, 65.4% +/- 2.5% of cervical cancer cases will develop one or more indications for RT at some point in the course of the illness, 63.4% +/- 2.3% will develop indications for RT as part of their initial management, and 2.0% +/- 0.9% will develop indications for RT for progressive or recurrent disease. The effects of variations in case mix on the need for RT was examined by sensitivity analysis, which suggested that the maximum plausible range for the appropriate rate of utilization of RT was 54.3% to 67.9%. The proportion of cases that required RT was stage dependent: 10.6% +/- 1.2% in Stage IA, 74.9% +/- 1.3% in Stage IB, 100% in Stages II and III, and 97.2% +/- 1.1% in Stage IV. CONCLUSIONS: This evidence-based estimate of the appropriate rate of use of RT for cervical cancer adds to the growing pool of knowledge about the need for RT that will ultimately provide a rational basis for long-term planning for RT programs and for auditing access to RT in the general population.     

Projecting the number of patients with colorectal carcinoma by phases of care in the US: 2000–2020

Objective This study provides projections of colorectal cancer prevalence by phases of care (initial, monitoring, and last year of life) to the year 2020 and describes the estimation method. Methods Cancer prevalence by phase of care was estimated from colorectal cancer incidence and survival from the Surveillance, Epidemiology, and End Results (SEER) Program data, population estimates and projections from the US Census Bureau, and all cause mortality data from the Human Mortality Life Tables. Assumptions of constant incidence and survival were used for projections from 2000 to 2020. Modeled and directly observed patient months by phase of care were compared for 1996 −1998 to provide validation of estimates. Results Prevalence of colorectal cancer is estimated to increase from 1,002,786 (0.36%) patients to 1,522,348 (0.46%) patients between 2000 and 2020. The estimated number of person-months in the initial and last year of life phases of care will increase 43%, while the monitoring phase of care will increase 54%. Modeled person-months by phase of care were consistent with directly observed measures of person months by phase of care in 1996–1998. Conclusions Under assumptions of current cancer control strategies we project that colorectal cancer prevalence will increase more rapidly than the US population, largely due to the aging of the US population. This suggests that considerable resources will be needed in the future for initial, continuing and last year of life treatment of colorectal cancer patients unless notable breakthroughs in primary prevention occur in the future years.     

Influence of tumor grade on time to progression after irradiation for localized ependymoma in children

PURPOSE: To investigate the influence of histologic grade on progression-free survival (PFS) after irradiation (RT) for pediatric patients with localized ependymoma. METHODS AND MATERIALS: Fifty patients with localized ependymoma (median age 3.6 years, range 1-18 years at the time of RT) were treated with RT between December 1982 and June 1999. Anaplastic features were identified in 14 of 50 patients. The extent of resection was characterized as gross-total in 36 patients, near-total in 5, and subtotal in 9. The median dose to the primary site was 54 Gy. Of the 50 patients, 23 received pre-RT chemotherapy. RESULTS: Thirty-nine patients were alive at a median follow-up of 46 months (range 21-214) from diagnosis. Thirty-four patients remained progression free at a median follow-up of 35 months (range 13-183) after the initiation of RT. Progression occurred in 16 patients (12 local and 4 local and distant), with a median time to failure of 21.2 months (range 4.6-65.0). The tumor grade significantly influenced the PFS after RT (p < 0.0005). The estimated 3-year PFS rate was 28% +/- 14% for patients with anaplastic ependymoma compared with 84% +/- 8% for patients with differentiated ependymoma. These results remained significant when corrected for age at diagnosis (<3 years), pre-RT chemotherapy, and extent of resection. Patients who received pre-RT chemotherapy had an inferior 3-year PFS estimate after RT (49 +/- 12%) compared with those who did not (84% +/- 10%; p = 0.056). Anaplastic ependymoma was found more frequently in the supratentorial brain (p = 0.002). Six of 12 patients with supratentorial tumor developed recurrence; recurrence was restricted to patients with anaplastic ependymoma. CONCLUSION: Tumor grade influences outcome for patients with ependymoma independent of other factors and should be considered in the design and analysis of prospective trials involving pediatric patients treated with RT. Chemotherapy before RT influences the PFS and overall survival after RT. The effect is more pronounced when progression occurs during chemotherapy.     

结直肠癌根治性手术后复发时间与生存时间的相关性分析

背景与目的：结直肠癌根治性手术后复发率达30%~40%,肿瘤复发影响患者生存时间。本研究旨在探讨结直肠癌复发时间(time to relapse,TTR)与肿瘤临床病理参数的关系,并进一步分析TTR对复发后生存时间的影响。方法：分析辽宁省肿瘤医院收治的375例结直肠癌患者的临床资料、病理结果及随访数据,比较结直肠癌复发与临床资料和病理类型的相关性,并研究TTR与复发后总体生存时间的关系。结果：TTR与确诊时肿瘤分期以及有无肺、肝脏转移密切相关。短期复发(<2年)与生存时间密切相关,2~5年内复发与5年以上复发的患者,其生存时间差异无统计学意义(P>0.05)。结论：结直肠癌患者术后复发时间与肿瘤分期及有无肺、肝脏转移密切相关,短期复发是预测复发后生存时间的重要指标。     

A population-based study of radiotherapy in a cohort of patients with rectal cancer diagnosed between 1996 and 2000.

AIMS: To study, in a population-based setting, the use of delayed radiotherapy (RT) in a cohort of 2008 unselected rectal cancer patients diagnosed between 1996 and 2000. PATIENTS AND METHODS: Radiation within 6 months of diagnosis was considered part of the primary treatment (PRT). RT given 6 months or later after diagnosis or after PRT was considered as delayed or secondary RT (SRT). Number, percentage and cumulative proportion of patients receiving SRT were calculated. The odds for receiving SRT (total and for recurrent rectal cancer only) were studied by logistic regression analysis, taking into account age, gender, co-morbidity, socio-economic status, stage, prior PRT and RT department (2 departments, each serving general hospitals only). RESULTS: Forty-six percent of all newly diagnosed patients received RT. Ten percent (n=203) received at least once SRT, either after PRT or as first RT, of which 96 patients for a relapsed rectal tumour (31 after PRT on the rectal tumour, 65 as a first radiation treatment). In a multivariate analysis of patients with rectal recurrence secondary pelvic irradiation was less often given after primary irradiation (OR: 0.7, 95% CI: 0.4-1.1). Patients with a stage III significantly more often received SRT on a recurrence (OR=2.5, 95% CI=1.4-4.5). Generally, patients in the eastern department received more often PRT and less often SRT for recurrence (OR: 0.5, 95% CI: 0.3-0.8). CONCLUSIONS: Five percent of all patients with rectal cancer received SRT on a recurrent tumour, with a large variation between the two RT departments in the region.     

Late recurrence from salivary gland cancer

BACKGROUND: The purpose of the current study was to determine the incidence of late recurrences, which were defined as those occurring >or=5 years after initial therapy, among patients treated for salivary gland cancer. METHODS: Between 1960 and 2000, 145 patients underwent definitive therapy for localized carcinomas of the salivary glands and were clinically without evidence of disease at 5 years of follow-up. Cumulative probabilities for developing a subsequent late recurrence were estimated using the Kaplan-Meier method. RESULTS: The 10-year and 15-year cumulative probabilities of late recurrence in patients who were free of disease at 5 years were 13% and 18%, respectively. The crude rates of late recurrence by histologic subtype were adenoid cystic carcinoma (26%), mixed malignant tumor (25%), mucoepidermoid carcinoma (17%), adenocarcinoma (10%), and acinic cell carcinoma (8%). Sites of late recurrence included distant metastasis (17 patients), local recurrence (8 patients), and regional recurrence (2 patients). The median time to late recurrence was 7.1 years (range, 5.2-23.1 years) from the date of initial surgery. Salvage treatment varied according to location of disease recurrence and initial treatment characteristics. The 15-year estimate of overall survival was 39% for patients who experienced a late recurrence compared with 71% for those who remained free of disease (P= .001). CONCLUSIONS: A significant proportion of patients who are presumed to be cured of their disease at 5 years after initial treatment for salivary gland cancer will be found to develop late disease recurrence with additional follow-up.     

Cyclooxygenase-2 expression as a predictor of para-aortic lymph node recurrence in uterine cervical cancer

PURPOSE: The overexpression of cyclooxygenase-2 (COX-2) is associated with a worse prognosis and the development of distant metastases in cervical cancer. This matched-pair analysis examined whether COX-2 expression is associated with para-aortic lymph node (PALN) recurrence in uterine cervical cancer treated with radiotherapy (RT). METHODS AND MATERIALS: For this study, we matched 20 patients with PALN recurrence after definitive or postoperative RT by stage with 20 others who did not have PALN recurrence. Of the 20 patients with PALN recurrence, definitive or postoperative RT was performed in 11 and 9 patients, respectively. COX-2 expression was assessed immunohistochemically using a mouse monoclonal antibody on formalin-fixed paraffin-embedded tumor specimens taken before RT. A logistic regression model was used to predict for PALN recurrence. RESULTS: COX-2 was expressed in 28 (70%) of the 40 patients. The staining intensity was as follows: weak in 19 (47%), moderate in 6 (15%), and strong in 3 (8%) patients. The patients with PALN recurrence had much greater expression of COX-2 (17 patients, 85%) than did the control group (11 patients, 55%; p = 0.04). Strong staining intensity of COX-2 was seen only in the PALN recurrence group. The statistically significant factors associated with PALN recurrence were positive pelvic lymph nodes (odds ratio, 7.61; 95% confidence interval, 1.55-37.37; p = 0.01) and COX-2 expression (odds ratio, 1.47; 95% confidence interval, 1.04-2.09; p = 0.03). CONCLUSION: Our findings suggest that COX-2 overexpression in the initial tumor tissue might be associated with PALN recurrence after RT in cervical cancer patients.     

FoxM1在结直肠癌中的表达及其临床意义

目的：探讨 FoxM1（fork head box M1）在结直肠癌（CRC）中的表达情况及其临床意义。方法：采用PCR（qRT －PCR）及免疫组化检测80例结直肠癌及对应癌旁组织中 FoxM1的水平,分析 FoxM1表达与临床病理参数及预后的关系。结果：结直肠癌组织中 FoxM1的相对表达量为1．326±0．018,高于癌旁结直肠组织的 FoxM1水平0．612±0．036（P ＜0．05）。免疫组化示结直肠癌组织中 FoxM1表达水平（70．0％,56／80）明显高于癌旁结直肠组织（12．5％,10／80）（P ＜0．05）,且其表达水平与肿瘤病理分期、Dukes 分级、淋巴结转移、肝脏转移均有关（P ＜0．05）。FoxM1表达阴性者的无瘤生存率明显高于表达阳性者,差异有统计学意义（P ＝0．002）。结论：FoxM1在结直肠癌组织的表达对预测 CRC 患者无瘤生存期及总生存期有重要意义。     

Population carrier frequency of hMSH2 and hMLH1 mutations

Knowledge of population carrier frequency for DNA mismatch repair (MMR) gene mutations would contribute to understanding the burden of cancer due to genetic susceptibility, but robust prevalence estimates are lacking. To estimate carrier frequency, we genotyped a cohort of relatives of mutation carriers and determined their colorectal cancer prevalence. Systematic Finnish and US data were combined with Scottish genotype and cancer prevalence data in a Bayesian calculation. The estimated carrier prevalence in the population aged 15-74 years is 1:3139 (95% Cl = 1:1247-1:7626) and these carriers are at high risk of colorectal and other cancers.     

Definitive radiotherapy for patients with isolated vaginal recurrence of endometrial carcinoma after hysterectomy

PURPOSE: To determine the outcome of patients after radical radiotherapy (RT) for isolated vaginal recurrence of endometrial carcinoma and to determine the clinical and pathologic predictors of outcome. METHODS AND MATERIALS: We reviewed the records of 91 patients treated at our institution between 1960 and 1997 with radical RT for vaginal recurrence after definitive surgery for endometrial carcinoma. Thirty-one percent of the patients received external beam RT (EBRT) alone, 12% received brachytherapy alone, and 57% received a combination. The median dose of radiation was 75 Gy (range 34-122). All end points were measured from the time of the first recurrence. The median duration of follow-up after recurrence was 58 months (range 1-289). RESULTS: The 2- and 5-year local control (LC) rate and overall survival rate was 82% and 75% and 69% and 43%, respectively. The median time from initial diagnosis of endometrial cancer to death from disease was 38 months. On univariate analysis, a dose to the relapse site of > or =80 Gy and EBRT plus brachytherapy vs. single-modality therapy were significant predictors of improved LC. On multivariate analysis, only the type of treatment correlated significantly with LC (p = 0.03). On univariate analysis, Grade 1 or 2 vs. Grade 3 tumor and EBRT plus brachytherapy vs. single-modality therapy were significant predictors of improved overall survival. CONCLUSION: RT provides excellent LC of isolated vaginal recurrences of endometrial carcinoma, particularly when high doses are given using a combination of EBRT and brachytherapy. However, distant metastases frequently develop despite local disease control, contributing to a 5-year overall survival rate of <50%. For patients who have an isolated vaginal recurrence, the time from initial diagnosis of endometrial cancer to death from disease is usually >3 years. For this reason, in studies of adjuvant RT, long-term follow-up is required to permit evaluation of the impact of treatment on survival.     

First-line oral capecitabine therapy in metastatic colorectal cancer: a favorable safety profile compared with intravenous 5-fluorouracil/leucovorin.

PURPOSE: To evaluate the safety profile of capecitabine using data from a large, well-characterized population of patients with metastatic colorectal cancer treated in two phase II studies. In these trials, capecitabine achieved significantly superior response rates, equivalent time to disease progression and equivalent survival compared with 5-fluorouracil (5-FU)/leucovorin. PATIENTS AND METHODS: Patients (n = 1207) were randomized to either oral capecitabine (1250 mg/m2 twice daily, on days 1-14 every 21 days) or intravenous (i.v.) bolus 5-FU/leucovorin (Mayo Clinic regimen). RESULTS: Capecitabine demonstrated a safety profile superior to that of 5-FU/leucovorin, with a significantly lower incidence of diarrhea, stomatitis, nausea, alopecia and grade 3 or 4 neutropenia leading to significantly fewer neutropenic fever/sepsis cases and fewer hospitalizations. All patients in the capecitabine group received a starting dose of 1250 mg/m2 twice daily and the majority (66%) did not require dose modification for adverse events. In the 5-FU/leucovorin group, 58% of patients did not require dose reduction for toxicities. The capecitabine dose-modification scheme reduced the recurrence of key toxicities without compromising efficacy. In both treatment arms, patients with moderate renal impairment at baseline (estimated creatinine clearance 30-50 ml/min) experienced a higher incidence of grade 3 or 4 toxicities. This increase was more pronounced with 5-FU/leucovorin. CONCLUSIONS: Capecitabine is at least as effective, better tolerated and more convenient than i.v. 5-FU/leucovorin as treatment for patients with metastatic colorectal cancer. Analysis of data from two large phase III trials demonstrates that efficacy is not compromised in patients requiring a dose reduction for adverse events. The phase III data and an additional pharmacokinetic study support a lower starting dose in patients with moderate renal impairment at baseline (calculated creatinine clearance 30-50 ml/min) and a contra-indication in patients with severely impaired creatinine clearance at baseline (<30 ml/min). For patients with normal or mildly impaired renal function at baseline, the standard starting dose is well tolerated. The incidence and severity of adverse events in patients with moderate renal impairment at baseline who were treated with 5-FU/leucovorin was more pronounced, indicating that capecitabine provides a better-tolerated alternative.     

Multi-institutional review of repeat irradiation of chest wall and breast for recurrent breast cancer

PURPOSE: To review the toxicity and clinical outcomes for patients who underwent repeat chest wall or breast irradiation (RT) after local recurrence. METHODS AND MATERIALS: Between 1993 and 2005, 81 patients underwent repeat RT of the breast or chest wall for locally recurrent breast cancer at eight institutions. The median dose of the first course of RT was 60 Gy and was 48 Gy for the second course. The median total radiation dose was 106 Gy (range, 74.4-137.5 Gy). At the second RT course, 20% received twice-daily RT, 54% were treated with concurrent hyperthermia, and 54% received concurrent chemotherapy. RESULTS: The median follow-up from the second RT course was 12 months (range, 1-144 months). Four patients developed late Grade 3 or 4 toxicity. However, 25 patients had follow-up >20 months, and no late Grade 3 or 4 toxicities were noted. No treatment-related deaths occurred. The development of Grade 3 or 4 late toxicity was not associated with any repeat RT variables. The overall complete response rate was 57%. No repeat RT parameters were associated with an improved complete response rate, although a trend was noted for an improved complete response with the addition of hyperthermia that was close to reaching statistical significance (67% vs. 39%, p = 0.08). The 1-year local disease-free survival rate for patients with gross disease was 53% compared with 100% for those without gross disease (p < 0.0001). CONCLUSIONS: The results of our study have shown that repeat RT of the chest wall for patients with locally recurrent breast cancer is feasible, because it is associated with acceptable acute and late morbidity and encouraging local response rates.     

Long-term oncologic results of salvage radical prostatectomy for locally recurrent prostate cancer after radiotherapy

PURPOSE: Salvage radical prostatectomy (RP) may potentially cure patients who have isolated local prostate cancer recurrence after radiotherapy (RT). We report the long-term cancer control associated with salvage RP in a consecutive cohort of patients and identify the variables associated with disease progression and cancer survival. METHODS AND MATERIALS: A total of 100 consecutive patients underwent salvage RP with curative intent for biopsy-confirmed, locally recurrent, prostate cancer after RT. Disease progression after salvage RP was defined as a prostate-specific antigen (PSA) level of > or =0.2 ng/mL or by initiation of androgen deprivation therapy. Cancer-specific mortality was defined as active clinical disease progression despite castration. Cox regression analysis was used to evaluate these endpoints. The median follow-up from RT was 10 years (range, 3-27 years) and from salvage RP was 5 years (range, 1-20 years). RESULTS: Overall, the 5-year progression-free probability was 55% (95% confidence interval, 46-64%), and the median progression-free interval was 6.4 years. The preoperative PSA level was the only significant pretreatment predictor of disease progression in the multivariate analysis (p = 0.01). The 5-year progression-free probability for patients with a preoperative PSA level of <4, 4-10, and >10 ng/mL was 86%, 55%, and 37%, respectively. The 10-year and 15-year cancer-specific mortality after salvage RP was 27% and 40%, respectively. The median time from disease progression to cancer-specific death was 10.3 years (95% confidence interval, 7.6-12.9). After multivariate analysis, the preoperative serum PSA level and seminal vesicle or lymph node status correlated independently with disease progression. CONCLUSIONS: Greater preoperative PSA levels are associated with disease progression and cancer-specific death. Long-term control of locally recurrent prostate cancer after definitive RT is possible when salvage RP is performed early in the course of recurrent disease.     

Irinotecan combined with bolus 5-fluorouracil and folinic acid Nordic schedule as first-line therapy in advanced colorectal cancer.

BACKGROUND: This multicentre phase II study evaluated the efficacy and safety of irinotecan combined with the Nordic schedule of 5-fluorouracil (5-FU) and folinic acid (FA) as first-line therapy in patients with advanced colorectal cancer. PATIENTS AND METHODS: Seventy-four patients with measurable disease and a WHO performance status of 2 or less were treated with irinotecan 210 mg/m(2) as a 30-90 min intravenous infusion on day 1, followed by 5-FU 500 mg/m(2) and FA 60 mg/m(2) bolus on days 1 and 2, every 2 weeks, until disease progression or unacceptable toxicity. The primary end point was the objective response rate. RESULTS: Twenty-nine out of 68 evaluable patients achieved a complete (n = 7) or partial (n = 22) response, leading to an overall response rate of 43% [95% confidence interval (CI) 31% to 55%]. The median duration of response was 10 months. The estimated median time to progression and survival were 6.4 months (95% CI 5.4-9.0) and 15.6 months (95% CI 13.3-19.0), respectively, in the intention-to-treat population. A total of 860 cycles were administered to 74 patients. Neutropenia was the main adverse event with grade 3-4 toxicity in 66% of patients and 17.5% of cycles. Grade 3-4 non-haematological toxicities were infrequent and included diarrhoea in 16% of patients and 2% of cycles and nausea/vomiting in 10% of patients and 1% of cycles. CONCLUSIONS: Irinotecan combined with the bolus Nordic schedule of 5-FU/FA is active in advanced colorectal cancer with an easily managed safety profile which ensures good schedule compliance. The low incidence of grade 3-4 non-haematological toxicity justifies the further evaluation of this combination in the context of randomised clinical trials.     

Geometric shifting of the porta hepatis during posthepatectomy radiotherapy for biliary tract cancer

PURPOSE: To evaluate geometric shifting of the porta hepatis induced by liver regeneration during radiotherapy (RT) after partial hepatectomy for biliary tract cancer. METHODS AND MATERIALS: Between August 2004 and August 2005, the study enrolled 10 biliary tract cancer patients who underwent hemihepatectomy or more extensive surgery and were scheduled to receive postoperative RT. All patients received 4500 cGy RT in 25 fractions with concurrent 5-fluorouracil. Before RT and in the third and fifth weeks during RT, the liver volume was determined using CT, and geometric location of the porta hepatis was determined using a conventional simulator. RESULTS: The liver volume increase during RT was 246.6 +/- 118.2 cm(3). The overall actual shifting length of the porta hepatis was 9.8 +/- 2.5 mm, with right and left hepatectomy causing a 10.1 +/- 1.7 mm shift to the right or 9.2 +/- 4.3 mm shift to the left, respectively. The actual shifting length of the porta hepatis was proportional to the increase in liver volume during RT (r = 0.742, p = 0.014). CONCLUSION: The results of this study have demonstrated that the porta hepatis can be shifted by liver regeneration after partial hepatectomy. We recommend an additional RT margin or adaptive RT (repeat planning at several intervals during the treatment course) to avoid exclusion of the porta hepatis from the RT target volume after partial hepatectomy for biliary tract cancer.     

Disease control intervals in high-risk neuroblastoma

BACKGROUND: Current salvage therapy for recurrent high-risk neuroblastoma is rarely curative. Assessment of the effectiveness of new, primarily cytostatic agents requires the redefinition of study endpoints to reflect disease stabilization rather than tumor response or regression. The intervals of disease control in the patients in the current study with recurrent neuroblastoma were characterized to provide comparison criteria for exploratory studies of new agents. METHODS: Disease control intervals, disease-free survival, postrecurrence survival, and median time to treatment failure were estimated in 90 patients with high-risk neuroblastoma treated between January 1991 and June 2002 on 3 St. Jude neuroblastoma protocols. RESULTS: The estimated median time to disease recurrence was 18.3 months (95% confidence interval [95% CI], 15.9-22.4 months) for the first recurrence, 8.7 months (95% CI, 5.0-12.2 months) for the second recurrence, and 3.8 months (95% CI, 2.5-5.4 months) for the third recurrence. The 5-year estimate of survival after the first disease recurrence was 11%+/-4%. Patients with longer initial disease control had a postrecurrence survival advantage:the 5-year estimated postrecurrence survival was 15.3%+/-6.3% for patients with initial disease control>or=16 months and 8.1%+/-5.5% for others (P=.006). The median disease control interval was approximately halved after each disease recurrence. CONCLUSIONS: The previous disease control interval should be considered in stratification schemes for future phase 2 testing of new agents for the treatment of neuroblastoma. For the optimal evaluation of new treatment strategies that incorporate cytostatic agents, study design and selection of endpoints must take into account the current patterns of recurrence or progression of neuroblastoma.     

Rectal cancer delivery of radiotherapy in adequate time and with adequate dose is influenced by treatment center, treatment schedule, and gender and is prognostic parameter for local control: results of study CAO/ARO/AIO-94

PURPOSE: The impact of the delivery of radiotherapy (RT) on treatment results in rectal cancer patients is unknown. METHODS AND MATERIALS: The data from 788 patients with rectal cancer treated within the German CAO/AIO/ARO-94 phase III trial were analyzed concerning the impact of the delivery of RT (adequate RT: minimal radiation RT dose delivered, 4300 cGy for neoadjuvant RT or 4700 cGy for adjuvant RT; completion of RT in <44 days for neoadjuvant RT or <49 days for adjuvant RT) in different centers on the locoregional recurrence rate (LRR) and disease-free survival (DFS) at 5 years. The LRR, DFS, and delivery of RT were analyzed as endpoints in multivariate analysis. RESULTS: A significant difference was found between the centers and the delivery of RT. The overall delivery of RT was a prognostic factor for the LRR (no RT, 29.6% +/- 7.8%; inadequate RT, 21.2% +/- 5.6%; adequate RT, 6.8% +/- 1.4%; p = 0.0001) and DFS (no RT, 55.1% +/- 9.1%; inadequate RT, 57.4% +/- 6.3%; adequate RT, 69.1% +/- 2.3%; p = 0.02). Postoperatively, delivery of RT was a prognostic factor for LRR on multivariate analysis (together with pathologic stage) but not for DFS (independent parameters, pathologic stage and age). Preoperatively, on multivariate analysis, pathologic stage, but not delivery of RT, was an independent prognostic parameter for LRR and DFS (together with adequate chemotherapy). On multivariate analysis, the treatment center, treatment schedule (neoadjuvant vs. adjuvant RT), and gender were prognostic parameters for adequate RT. CONCLUSION: Delivery of RT should be regarded as a prognostic factor for LRR in rectal cancer and is influenced by the treatment center, treatment schedule, and patient gender.