Carcinoma of the uterine cervix. I. Impact of prolongation of overall treatment time and timing of brachytherapy on outcome of radiation therapy

: Some studies have described pelvic tumor control and survival rates in invasive carcinoma of uterine cervix when the overall time in a course of definitive irradiation is prolonged. We attempt to confirm or deny these observations and evaluate the impact of timing of brachytherapy on outcome. We also explore the hypothesis that more extensive tumors technically require prolongation of the course of irradiation; thus decreased tumor control and survival in these patients may not necessarily be the result of time/dose factor. : Records of 1224 patients (Stage IB to III) treated with definitive irradiation (combination of external beam and two intracavitary insertions to deliver doses of 70 to 90 Gy to point A) were reviewed. Follow-up was obtained in 97% of the patients (median, 12 years; minimum, 3 years; maximum, 28 years). The relationship between outcome and overall treatment and time of intracavitary insertions was analyzed in each stage and according to tumor size/extent. : There was strong correlation between overall treatment time (OTT) and tumor stage (≤ 7 weeks: 81% for Stage IB; 74% for Stage IIA; 52% for Stage IIB; and 47% for Stage III). Interuptions of therapy accounting for prolongation of treatment time ocurred in 25–30% of patients, most frequently because of holidays and weekends and side effects of therapy. Overall treatment time had a major impact on pelvic tumor control in Stages IB, IIA, and IIB; in Stage IB 10-year actuarial pelvic failure rates were 7% with OTT ≤ 7 weeks, 22% with 7.1 to 9 weeks, and 36% with >9 weeks (p ≤ o.01). For Stage IIA the corresponding values were 14%, 27% and 36% (p = 0.08), and in Stage IIB pelvic failure rates were 20%, 28%, and 34%, respectively (p = 0.09). In Stage III, pelvic failure was 30%, 40%, and 505 respectively (p = 0.08). There was also a strong correlation between OTT and 10-year cause-specific survival (CSS); in Stage IB rates were 86% with OTT of ≤7 weeks, 78% for 7.1 to 9 weeks, and 55% for ≥9 weeks (p < 0.01). The corresponding rates in Stage IIA were 73%, 41%, and 48% (p ≤ 0.01). For patients with Stage IIB, CSS rates were 72% for OTT ≤7 weeks, 60% for 7.1 to 9 weeks, and 70 for >9 weeks (p = 0.01). Patients with Stage III disease had 45% to 10-year CSS when treatment was delivered in 9 weeks or less and 36% for longer overall (p = 0.16). In multivariate analysis of patients with Stage IB and IIA, OTT and clinical stage were the most important prognostic factors for pelvic tumor control, disease-free survival, and CSS. Tumor size was a prognostic factor for CSS. In Stages IIB and III, OTT, clinical stage, unilateral or bilateral parametrical invasion, and dose to point A were significant prognostic factors for pelvic tumor control, disease-free survival, and CSS. Prolongation of time had a significant impact on pelvic tumor control and CSS regardless of tumor size, except in Stage IB tumors ≤3 cm. Regression analysis confirms previous reports that prolongation of OTT results in decreased pelvic tumor control rate of 0.85% per day for all patients, 0.37% per day in Stages IB and IIA, 0.68% per day in Stage IIB, and 0.54% for Stage III patients treated with ≥85 Gy to point A. Performance of all intracavity insertions within 4.5 weeks from initiation of irradiation of yeilded decreased pelvic failture rates in some groups of patients (8.8 vs. 18% in Stage IB and IIA tumors ≤4 cm and 12.3 vs. 35% in Stage IBB) (p ≤ 0.01). : Prolongation of treatment time in patients with Stage IB, IIA, IIB, and III carcinoma of the uterine cervix has a significant impact on pelvic tumor control and CSS. The effect of OTT was present regardless of tumor size except in Stage IB tumors ≤3 cm. This may be related to biologic factors such as cell repopulation and increased proliferation resulting from treatment interruptions, in addition to initial clonogenic cells burden. Irradiation for patients with invasive carcinoma of the cervix should be delivered in the shortest possible overall time.     

非小细胞肺癌放疗总疗程时间对疗效的影响

回顾性分析根治性放疗的非小细胞肺癌病例,探讨总疗时间对放疗效果的影响。材料与方法,选择１９９０年１月－１９９６年１２月间根治性放疗的经病确诊的Ⅰ－Ⅲｂ期与ＮＳＣＬＣ患者２５６例,生存统计采用Ｋａｐｌａｎ－Ｍｉｅｒｅ法及Ｌｏｇ－ｒａｎｋ检验,     

The impact of overall treatment time on outcomes in radiation therapy for non-small cell lung cancer

PURPOSE: A retrospective study was carried out to evaluate the impact of overall treatment time (OTT) on the results of radiation therapy for non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: From Jan. 1990 to Dec. 1996, 256 patients with stages I-IIIb NSCLC entered this analysis. All patients received definitive radiotherapy. Biologically effective dose (BED) was used to standardize the irradiation effects. The correlation between OTT and local progression-free survival was analyzed by linear-regression and Cox proportional hazard models. The prognostic variables for survival and distant metastasis were also briefly studied. RESULTS: OTT had been shortened in 64 patients because of an accelerated hyperfractioned irradiation, while OTT was prolonged i n 114 patients due to interruptions of irradiation courses. The main ca uses of interruption were machine breakdown or delayed preparations of c errobend block for boost fields (55%), holidays (11%) and treatment toxi city and side effects (34%).Patients tre ated with prolonged OTT (> 45 days) had significant poorer local progression-free survival than whom with OTT of 相似文献   

放射治疗时间与中晚期宫颈癌预后关系的研究

目的 研究中晚期宫颈癌单独放疗时总的放疗时间对治疗结果的影响。方法 选择1986～1990年治疗的386例Ⅱb和Ⅲ期宫颈癌患者进行外照射和腔内照射,对这些患者进行综合分析,确定总的放疗时间是否为影响预后的因素。结果 经过综合分析表明,宫颈癌放射治疗中总的治疗时间和输血是影响疗效的两个最具有显著意义的因素。治疗时间超过56 d时,每超过1 d,局部控制率和总生存率大约每天降低1％。结论 总的放射治疗时间是影响中晚期宫颈癌疗效的预后因素。     

Carcinoma of the cervix stage IB: Results of treatment with radiation therapy

An analysis has been made of 101 patients treated with radiation therapy for epidermoid carcinoma of the cervix Stage IB (FIGO) from January 1970 through December 1976. The patients were treated with a combination of intracavitary therapy and external beam therapy delivering a total combined dose of 8000 rad to the paracervical areas (Points A_R and A_L) and 5500 rad to the pelvic lymph nodes (Points I_R and I_L). The cumulative, disease-free survival at 2, 3 and 5 years was 89%, 87% and 84%. Sixteen failures were recorded in this group of patients, of which 3 were a result of loco-regional disease, 5 loco-regional disease plus distant metastasis and 8 distant metastasis only. The failure rate was greater among the patients who had lesions 4 or more cm in diameter and in patients who received doses of external beam therapy to the whole pelvis of 4000 rad or more. Eighteen patients developed complications; however, one patient had a recto-vaginal and a vesico-vaginal fistula; thus 19 complications were recorded. The complications were divided according to their severity into three groups: Grade I (mild) Grade If (moderate) and Grade III (severe). There were 10 Grade 1, 4 Grade II and 5 Grade III complications.     

Carcinoma of the cervix, stage III. Results of radiation therapy

From April 1969 through December 1980, 203 patients with Stage III epidermoid carcinoma of the cervix were treated with radiation therapy with curative intent. The disease-free survival at 2, 5, and 10 years was 50%, 33%, and 27%, respectively. The survival was better for patients with Stage IIIB disease than for those with Stage IIIA disease. Eighty-eight patients were treated with external beam therapy only, and 115 received external beam and brachytherapy. The disease-free survival was better for the combination therapy group initially, but this difference was not sustained beyond 5 years. One hundred eight patients experienced recurrence within the irradiated field, for a locoregional recurrence rate of 53%. Twenty-seven patients had complications (13%). The complications were mild in 13 patients, moderate in 4 patients, and severe in 10 patients. A study was made of the relationship of the dose to Point A and the occurrence of complications. Similar analyses were made of the bladder and rectal doses and the subsequent occurrence of urinary and intestinal complications. In these analyses, the mean dose to Point A and the critical organs was higher for the groups of patients with complications than for those patients without complications. This relationship was also observed when the patients were stratified for treatment with either external beam plus brachytherapy or external beam therapy alone.     

The impact of the time to start radiation therapy on overall survival in newly diagnosed glioblastoma

Journal of Neuro-Oncology - We sought to determine which therapeutically targetable immune checkpoints, costimulatory signals, and other tumor microenvironment (TME) factors are independently...     

Radiation therapy morbidity in carcinoma of the uterine cervix: dosimetric and clinical correlation.

PURPOSE: To quantitate the impact of total doses of irradiation, dose rate, and ratio of doses to bladder or rectum and point A on sequelae in patients treated with irradiation alone for cervical cancer. METHODS AND MATERIALS: Records were reviewed of 1456 patients (Stages IB-IVA) treated with external-beam irradiation plus two low-dose rate intracavitary insertions to deliver 70 to 90 Gy to point A. Follow-up was obtained in 98% of patients (median, 11 years; minimum, 3 years; maximum, 30 years). The relationships among various dosimetry parameters and Grade 2 or 3 sequelae were analyzed. RESULTS: In Stage IB, the frequency of patients developing Grade 2 morbidity was 9%, and Grade 3 morbidity, 5%; in Stages IIA, IIB, III, and IVA, Grade 2 morbidity was 10% to 12% and Grade 3 was 10%. The most frequent Grade 2 sequelae were cystitis and proctitis (0.7% to 3%). The most common Grade 3 sequelae were vesicovaginal fistula (0.6% to 2% in patients with Stage I-III tumors), rectovaginal fistula (0.8% to 3%), and intestinal obstruction (0.8% to 4%). In the bladder, doses below 80 Gy correlated with less than 3% incidence of morbidity and 5% with higher doses (p = 0.31). In the rectosigmoid, the incidence of significant morbidity was less than 4% with doses below 75 Gy and increased to 9% with higher doses. For the small intestine, the incidence of morbidity was less than 1% with 50 Gy or less, 2% with 50 to 60 Gy, and 5% with higher doses to the lateral pelvic wall (p = 0.04). When the ratio of dose to the bladder or rectum in relation to point A was 0.8 or less, the incidence of rectal morbidity was 2.5% (8 of 320) vs. 7.3% (80 of 1095) with higher ratios (p < or = 0.01); bladder morbidity was 2.3% (7 of 305) and 5.8% (64 of 1110), respectively (p = 0.02). The incidence of Grade 2 and 3 bladder morbidity was 2.9% (10 of 336) when the dose rate was less than 0.80 Gy/h, in contrast to 6.1% (62 of 1010) with higher dose rates (p = 0.07). Rectal morbidity was 2% to 5% in Stage IB, regardless of dose rate to the rectum; in Stages IIA-B and III, morbidity was 5.2% (28 of 539) with a dose rate of 0.80 Gy or less and 10.7% (37 of 347) with higher dose rates (p < 0.01). Multivariate analysis showed that dose to the rectal point was the only factor influencing rectosigmoid sequelae, and dose to the bladder point affected bladder morbidity. CONCLUSIONS: Various dosimetric parameters correlate closely with the incidence of significant morbidity in patients treated with definitive irradiation for carcinoma of the uterine cervix. Careful dosimetry and special attention to related factors will reduce morbidity to the lowest possible level without compromising pelvic tumor control.     

Standardized radiation treatment method for carcinoma of the uterine cervix

Due to a world-wide information exchange on cancer therapy, a standardized treatment method for cancer is desirable. Radiation therapy for carcinoma of the uterine cervix is usually in combination with external and intracavitary irradiation. A basic treatment regiment for carcinoma of the uterine cervix with external and intracavitary irradiation was established by the major Japanese institutions. The consensus include: size and shape of irradiation field, dose, the reference from which to calculate the point A dose the external orifice of cervix is point A dose is regarded as the minor dose between right and left point As', categorized treatment methods with RALS according to cancer stage, the post operative irradiation method. This standardized treatment method will be applied for data analysis at each institution and will promote the further development of radiation therapy.     

Second cancer after radiation therapy for cancer of the uterine cervix

Radiation-induced cancers after radiation therapy for cancer of the uterine cervix were investigated on 11,855 patients including 5725 patients treated with radiation therapy alone, 1969 postoperative radiation therapy and 4161 surgery alone. The observed-to-expected ratios of the second primary cancer was 0.933 for the patients with radiation therapy alone and 1.074 for the patients with postoperative radiation therapy, respectively. No significant increase was observed in the risk of second primary cancers when all sites were combined. However, assessing on site by site basis, significant excess was noted for the rectum cancer, leukemia, and bladder cancer for the radiation therapy group but not for the surgery group. A significant excess of lung cancer was observed in both radiation therapy and surgery groups, which was attributed to some other causative factors. Radiation-induced cancers were suggested to develop apparently in organs involved in the irradiated field.     

Analysis of pelvic tumor control and impact on survival in carcinoma of the uterine cervix treated with radiation therapy alone

A total of 1054 patients with histologically confirmed invasive carcinoma of the uterine cervix were treated with radiation therapy alone between 1959 and 1982. All patients are available for a minimum of 3 years follow-up. Radiation therapy consisted of external irradiation to the whole pelvis (1000-2000 cGy) and parametria (for a total of 4000-6000 cGy) combined with two intracavitary radioactive source insertions (6000-7500 cGy to point A). Patients with Stage IIB, III, and IVA have been consistently treated with somewhat higher doses of external irradiation and intracavitary insertions. A small group of 54 patients with Stage IIB or IIIB had pelvic lymphadenectomy following the irradiation (1960-1964). There was a strong correlation between the tumor regression within 30 days from completion of radiotherapy and the incidence of pelvic recurrences or distant metastases for each of the anatomical stages. The 10-year survival rate for Stage IB was 76%, Stage IIA 60%, Stage IIB 45%, and Stage III 25%. Many of the deaths were due to intercurrent disease. Thus, the 10-year tumor-free survival was 80% for Stage IB, 60% for Stages IIA and IIB and 35% for Stage III. In Stage IB total doses of 6000 cGy or higher to point A resulted in 94% pelvic tumor control. In Stage IIA, the pelvic tumor control was 87% with doses of 6000 cGy to point A or higher. However, in Stage IIB the pelvic tumor control was 58% with doses below 6000 cGy, 78% with 6001-7500 cGy and 82% with higher doses. In Stage IIIB the pelvic tumor control was 42% with doses below 6000 cGy, 57% with 6001-7500 cGy and 68% with higher doses. Tumor control in the pelvis was correlated with the following 5 year survivals: Stage IB-95% (353 patients); Stage IIA-84% (116 patients); Stage IIB-84% (308 patients); Stage IIIB-74% (245 patients). The 5-year survival for patients that recurred in the pelvis was 30% for Stage IB, about 15% for Stages IIA-B and only 5% in Stage III. Patients with tumor control in the pelvis had a significantly lower incidence of distant metastases than patients who initially failed in the pelvis (9.3% vs. 58.6% in Stage IB, 21.6% vs 52.6% in Stage IIA, 19.8% vs 16.7% in Stage IIB, and 31.2% vs 50% in Stage III). In Stage IIB the figures were 19.8% and 16.7% because the initial pelvic recurrence was frequently concurrent with distant metastases.(ABSTRACT TRUNCATED AT 400 WORDS)     

Uncertainties in radiation therapy: target definition in carcinoma of the uterine cervix

In treatment of patients with carcinoma of the cervix, as in any other malignant tumor, accurate identification of target volumes is critical to enhance precision of radiation therapy planning and delivery. These results in improved locoregional tumor control lead to lower incidence of distant metastases and improved survival. Also, radiation therapy morbidity is decreased, enhancing quality of life. Various imaging techniques are available to achieve better target delineation and this can be enhanced with image fusion. Available innovative treatment techniques to optimize the use of radiation therapy for these patients are illustrated.     

Radiation therapy for T1,2 glottic carcinoma: impact of overall treatment time on local control

Purpose: Local control probabilities of T1,2 glottic laryngeal cancer were evaluated in relation to dose and fractionation of radiation therapy (RT). Materials and methods: Between 1975 and 1993, 96 T1N0M0 glottic cancers and 32 T2N0M0 glottic cancers were treated with definitive RT. Total RT dose was 60–66 Gy/2 Gy for most of the T1 and T2 tumors, although 10 T2 tumors were treated with hyperfractionation (72–74.4 Gy/1.2 Gy bid). Of the 128 patients, 90 T1 glottic tumors and 30 T2 glottic tumors were followed for >2 years after treatment. Multivariate analyses using the Cox proportional hazards model and a logistic regression analysis were performed to evaluate the significance of prognostic variables on local control. Results: The 5-year local control probability for T1 tumors was 85%, whereas that for T2 tumors was 71%. Multivariate analyses demonstrated that only overall treatment time (OTT) was a significant variable for local control. Total RT dose, normalized total doses at a fraction size of 2 Gy, and fraction size were not significant. Local control probability of T1 tumors with an OTT of 42–49 days was significantly higher than that of tumors with an OTT of >49 days (P < 0.02). Only a 1-week interruption of RT, due to holidays, significantly reduced the 5-year local control probability of T1 glottic tumors from 89 to 74% (P < 0.05). Conclusions: These results indicate that OTT is a significant prognostic factor for local control of T1 glottic tumors.