High dose-rate brachytherapy for elderly patients with uterine cervical cancer

BACKGROUND: The need for radiotherapy (RT) in cancer treatment for the elderly patient is growing. The purpose of this study was to analyze the efficacy and complication rate for radiotherapy, using external-beam irradiation (EBRT) and high dose-rate intracavitary brachytherapy (HDRICB), for patients aged 70 years or older with carcinoma of the uterine cervix. METHODS: From September 1992 to December 1997, 295 patients diagnosed with uterine cervical cancer completed RT at the Shin Kong Memorial Hospital and China Medical College Hospital. Two hundred and fifty-eight patients [International Federation of Gynecology and Obstetrics (FIGO) stage distribution: 35 Ib, 26 IIa, 122 IIb, 10 IIIa, 58 IIIb, 7 IVa] who had undergone at least two courses of HDRICB and a minimum of 3 years of follow-up, were evaluated. A retrospective analysis was conducted to compare the outcome of radiation therapy for the 179 patients under 70 years of age (younger group) and the 79 patients aged 70 years or older (older group). The RT consisted of EBRT followed by HDRICB. After a total EBRT dose of 40-45 Gy/20 in 25 fractions, irradiating the whole pelvis over 4-5 weeks, dosage for patients diagnosed as FIGO stage IIb-IVa bilateral parametrial disease was boosted to 54-58 Gy, with central shielding. HDRICB was administered at 1-week intervals using an Ir-192 remote after-loading technique. Ninety-nine patients (38.4%) received three fractions of HDRICB, while 156 patients (60.5%) had four fractions. Total prescribed Point A dosages (EBRT + HDRICB) ranged from 58 to 71.6 Gy (median, 65.6 Gy) for stage IB-IIA, while for larger lesions (stage IIB-IVA) analogous dosages were 59-75.6 Gy (median, 65.6 Gy). Median follow-up durations for the older and younger groups were 56/55 months, respectively. RESULTS: The respective 5-year actuarial survivals (AS) for the older and younger groups were 82/85% for stage Ib, 65/65% for IIa, 61/71% for IIb and 35/59% for IIIa-b. The 5-year cause-specific survivals (CSS) for the older and younger groups were 100/95% for stage Ib, 85/75% for IIa, 78/72% for IIb and 42/61% for IIIa-b. The 5-year pelvic relapse-free survivals (PRFS) for the older and younger groups were 100/100% for stage Ib, 91/93% for IIa, 91/90% for IIb and 67/80% for IIIa-b. The 5-year distant metastasis-free survivals (DMFS) for older and younger groups were 100/100% for stage Ib, 92/88% for IIa, 84/73% for IIb and 55/75% for IIIa-b. There was no statistically significant survival difference on comparing the two groups according to stage. The gross tumor-free ratios after EBRT (NRT) for the older and younger groups were 44.3/24.5% (P = 0.001). The 5-year CSS for the 35 NRT patients was 88% for the older group, while for the 44 patients diagnosed with gross residual tumor after EBRT (GRT) it was 64% (P = 0.001). Twelve (15.0%) of the 79 older patients and 14 (7.8%) of the 179 younger patients developed RTOG grade 3-4 rectal complications (P = 0.12), while seven (8.9%) of the 79 older patients and 10 (5.6%) of the 179 younger patients developed RTOG grade 3-4 small bowel complications (P = 0.34). CONCLUSION: Radiation therapy, consisting of a combination of EBRT and three or four fractions of HDRICB, proved to be effective for older patients. Further optimization of treatment policy is essential by changing the HDRICB fractionation strategy, shortening the treatment time and designing combination drug regimens that are both effective and tolerable during radiotherapy.     

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.     

The prediction of late rectal complications following the treatment of uterine cervical cancer by high-dose-rate brachytherapy

PURPOSE: This study aimed to correlate patient, treatment, and dosimetric factors with the risk of late rectal sequelae in patients with uterine cervical cancer treated with external beam radiation therapy (EBRT) and high dose rate intracavitary brachytherapy (HDRICB). METHODS AND MATERIALS: From September 1992 to December 1995, a total of 128 patients with uterine cervical cancer, who were treated and survived more than 12 months, were evaluated. After EBRT with 40-44 Gy/20-22 Fr/4-5 weeks to the whole pelvis, the dose was boosted up to 54-58 Gy with central shielding for patients with bilateral parametria of Stage IIb or greater. HDRICB consisted of three to four insertions at doses of 5-7.2 Gy (to Point A) at intervals of 1 week. Patient and treatment factors were analyzed using logistic regression analysis and the cumulative rectal biologic equivalent dose (CRBED) was calculated. RESULTS: After 30-75 months of follow-up (median, 43 months), 38 patients (29.7%) had late rectal sequelae. Patients who had Stage IIb-IVa disease, cumulative rectal dose (external RT + total ICRU rectal dose) greeater than 65 Gy, or age greater than 70 years had a high risk of developing late rectal sequelae. When 110 Gy was used as the cut-off value, 19.6% (10 of 51) of patients whose CRBED was less than 110 Gy had rectal complications, while 36.4% (28/77) of patients whose CRBED was greater than 110 Gy developed rectal complications. CONCLUSION: Risk factors of late rectal complications were advanced stage, age greater than 70 years, and cumulative rectal dose of greater than 65 Gy.     

Clinical radiobiology of stage T2-T3 bladder cancer

PURPOSE: To evaluate the relationship between total radiation dose and overall treatment time (OTT) with the treatment outcome, with adjustment for selected clinical factors, in patients with Stage T2-T3 bladder cancer treated with curative radiotherapy (RT). METHODS AND MATERIALS: The analysis was based on 480 patients with Stage T2-T3 bladder cancer who were treated at the Center of Oncology in Gliwice between 1975 and 1995. The mean total radiation dose was 65.5 Gy, and the mean OTT was 51 days. In 261 patients (54%), planned and unplanned gaps occurred during RT. Four fractionation schedules were used: (1) conventional fractionation (once daily, 1.8-2.5 Gy/fraction); (2) protracted fractionation (pelvic RT, once daily, 1.6-1.7 Gy/fraction, boost RT, once daily, 2.0 Gy/fraction); (3) accelerated hyperfractionated boost (pelvic RT, once daily, 2.0 Gy/fraction; boost RT, twice daily, 1.3-1.4 Gy/fraction); and (4) accelerated hyperfractionation (pelvic and boost RT, twice daily, 1.2-1.5 Gy/fraction). In all fractionation schedules, the total radiation dose was similar (average 65.5 Gy), but the OTT was different (mean 53 days for conventional fractionation, 62 days for protracted fractionation, 45 days for accelerated hyperfractionated boost, and 41 days for accelerated hyperfractionation). A Cox proportional hazard model and maximum likelihood logistic model were used to evaluate the relationship between the treatment-related parameters (total radiation dose, dose per fraction, and OTT) and clinical factors (clinical T stage, hemoglobin level and bladder capacity before RT) and treatment outcome. RESULTS: With a median follow-up of 76 months, the actuarial 5-year local control rate was 47%, and the overall survival rate was 40%. The logistic analysis, which included the total dose, OTT, and T stage, revealed that all of these factors were significantly related to tumor control probability (p = 0.021 for total radiation dose, p = 0.038 for OTT, and p = 0.00068 for T stage). A multivariate Cox model, which included the treatment-related parameters and other clinical factors, revealed that the hemoglobin level and bladder capacity before RT and T-stage were statistically significant factors determining local control and overall survival. The total radiation dose was of borderline statistical significance for overall survival (p = 0.087), and OTT did not reach statistical significance. CONCLUSION: The results of our study showed that the treatment outcome after RT for bladder cancer depends mainly on clinical factors: hemoglobin level and bladder capacity before RT, and clinical T stage. An increase in the total radiation dose seemed to be associated with a better treatment outcome. The effect of the OTT was difficult to define, because it was influenced by other prognostic factors.     

Does initial 45Gy of pelvic intensity-modulated radiotherapy reduce late complications in patients with locally advanced cervical cancer? A cohort control study using definitive chemoradiotherapy with high-dose rate brachytherapy

Background

Comparing initial 45 Gy of pelvic intensity-modulated radiation therapy (IMRT) and non-IMRT in terms of the late toxicities associated with advanced cervical cancer that has also been treated with definitive concurrent chemoradiotherapy and high-dose rate intracavitary brachytherapy (HDRICB).

Patients and methods

This retrospective study included 320 stage IB2-IIIB cervical cancer patients treated with CCRT (83 IMRT and 237 non-IMRT). The two groups had similar stage and HDRICB ratings. Following 45 Gy to the pelvis, HDRICB of 24 Gy in four courses was prescribed. Late toxicities, including rectal complications (RC), bladder complications (BC) and non-rectal intestinal injury (NRRII), were scored by the Common Terminology Criteria for Adverse Events. A logistic regression was used to estimate the odds ratio (OR) of the complications.

Results

With a median follow-up duration of 33 and 77 months for IMRT and non-IMRT, 33 patients had Grade 2 or higher late RC (7.2% IMRT, 11.4% non-IMRT), whereas that for BC was 40 (9.6% IMRT, 13.5% non-IMRT) and for NRRII was 48 (12.0% IMRT, 16.0% non-IMRT). The cumulative rate for total grade 3 or higher gastrointestinal or genitourinary toxicities was 8.4% and 11.8% (p = 0.33). IMRT did not reduce the OR for all endpoints; however, the ORs for rectum and bladder reference doses to Point A were associated with RC and BC.

Conclusions

Locally advanced cervical cancer patients treated with initial 45Gy of pelvic IMRT and HDRICB have similar treatment-related late toxicities as those treated with non-IMRT. Optimization of the brachytherapy scheme is essential to minimize late toxicities.     

Treatment results and prognostic factors in inoperable carcinoma of the cervix treated with external plus high dose brachytherapy

Patients with inoperable carcinoma of the cervix treated with external plus high dose rate brachytherapy (HDRB), between 1988 and 1995 were evaluated retrospectively. According to stage, 5 year survival rates were 67.3% in stage IIb and 52.6% in stage III (P = 0001) and disease free survival (DFS) rates were 54.0% in stage IIb and 43.9% in stage III (P = 0.01). The following parameters were studied: age; stage; external beam dose; brachytherapy dose; total dose to point A; tumor mass; tumor response rate; bilateral or unilateral invasion of parametria in stage IIb; and bilateral or unilateral invasion of pelvic wall in stage IIIb; and the existence of hydronephrosis. The only significant parameter of 5 year survival and local control was tumor mass (P = 0.003).     

Influence of overall treatment time and radiobiological parameters on biologically effective doses in cervical cancer patients treated with radiation therapy alone

The aim of the study was to examine the influence of overall treatment time (OTT) on the value of calculated biological effective doses (BEDs) for different biological variables. These variables were: tumour proliferation rate, different cell radiosensitivity (alpha=0.2, 0.3, and 0.4 /Gy), and different start time for repopulation (Tk=21, 28, and 35 days). Also the influence of age (), Hb level (), tumor proliferation rate (bromodeoxyuridine labelling index; BrdUrdLI), and DNA ploidy on survival after shorter (60 days) OTT was investigated. The study included 229 patients with cervix carcinoma treated entirely by standard radiotherapy (RT) (external beam RT plus low-medium dose-rate (LDR/MDR) brachytherapy (BT) at the Center of Oncology in Krakow. The linear quadratic equation was used to calculate BED, which is proportional to log cell kill. BEDs 10 (for tumours) were calculated with consideration of OTT for each patient and tumour proliferation rate (standardized potential doubling time; standardized Tpot) based on BrdUrdLI assessed on biopsy material before RT. Median OTT was 90 days (range 30-210). The mean calculated total BED for point A for tumour and 'early reactions' was equal to 103.0 Gy10. The longest median survival time--52 months--was seen for patients treated with OTT 8.8%) BED loss was 1.4 Gy/day and for slowly proliferating tumours (BrdUrdLI 50 years (p=0.003) and high Hb level (>116 g/l) (p=0.041). For longer treatments (OTT >60 days) the unfavourable parameters were: age 相似文献   

High versus low dose rate intracavitary irradiation for adenocarcinoma of the uterine cervix.

BACKGROUND: Traditionally, low dose rate (LDR) brachytherapy has been used as a standard modality in the treatment of patients with carcinoma of the uterine cervix. The purpose of this work was to evaluate the effects of high dose rate (HDR) brachytherapy on patients with adenocarcinoma of the uterine cervix and to compare them with the effects of LDR brachytherapy. METHODS: From January 1971 to December 1992, 104 patients suffering from adenocarcinoma of the uterine cervix were treated with radiation therapy in the Department of Radiation Oncology, Yonsei University. LDR brachytherapy was carried out on 34 patients and HDR brachytherapy on 70 patients. In the LDR group, eight patients were in stage IB, six in IIA, 12 in IIB, three in IIIA and five in IIIB. External radiation therapy was delivered with 10 MV X-rays, 2 Gy fraction per day, total dose of whole pelvis 36-52 Gy (median 46 Gy). LDR radium intracavitary irradiation was performed with a Henschke applicator, 37-59 Gy targeted at point A (median 43 Gy). In the HDR group, there were 16 patients in stage IB, six in IIA, 32 in IIB and 16 in IIIB. The total whole pelvis dose of external radiation was 40-50 Gy (median 44 Gy), daily 1.8-2.0 Gy. HDR Co-60 intracavitary irradiation was performed with a remotely controlled after-loading system (RALS), 30-48 Gy (median 39 Gy) targeted at point A, three times per week, 3 Gy per fraction. RESULTS: The 5-year overall survival rate in the LDR group was 72.9, 61.9 and 35.7% in stage I, II and III, respectively and the corresponding figures for HDR were 87.1, 58.3 and 43.8% (p > 0.05). There was no statistical difference between the HDR group and the LDR group in terms of the 5-year overall survival rate from adenocarcinoma of the uterine cervix. There was a late complication rate of 12% in the LDR group and 27% in the HDR group. The incidence of late complications in stages II and III was higher in the HDR group than in the LDR group (31.6 vs 16.7% in stage II, 37.3% vs 12.5% in stage III, p > 0.05). No prognostic factors were evident in the comparison between the two groups. CONCLUSION: There was no difference in terms of 5-year survival rate in the patients with adenocarcinoma of the uterine cervix between those treated with HDR and those treated with LDR brachytherapy. Even though late complication rates were higher in the HDR group, most of them were classified as grade I. This retrospective study suggests that HDR brachytherapy may be able to replace LDR brachytherapy in the treatment of adenocarcinoma of the uterine cervix.     

Intravaginal brachytherapy alone for intermediate-risk endometrial cancer

PURPOSE: Despite the results of the Gynecologic Oncology Group trial No. 99 (GOG#99), some unanswered questions still remain about the role of adjuvant radiotherapy (RT) for intermediate-risk endometrial cancer. First, can intravaginal brachytherapy (IVRT) alone substitute for external beam RT but without added morbidity? Second, is the high-risk (HR) definition from GOG#99 a useful tool to predict pelvic recurrence specifically? The purpose of this study was to try to answer these questions in a group of patients with Stage IB-IIB endometrial carcinoma treated with high-dose-rate (HDR) IVRT alone. METHODS AND MATERIALS: Between November 1987 and December 2002, 382 patients with Stage IB-IIB endometrial carcinoma were treated with simple hysterectomy followed by HDR-IVRT alone at our institution. Comprehensive surgical staging (CSS), defined as pelvic washings and pelvic/paraaortic lymph node sampling, was performed in 20% of patients. The mean age was 60 years (range, 29-92 years). Lymphovascular invasion (LVI) was present in 14% of patients. The median HDR-IVRT dose was 21 Gy (range, 6-21 Gy), given in three fractions. Complications were assessed in terms of late Radiation Therapy Oncology Group (Grade 3 or worse) toxicity of the GI tract, genitourinary GU tract, and vagina. RESULTS: With a median follow-up of 48 months, the 5-year vaginal/pelvic control rate was 95% (95% confidence interval [CI], 93-98%). On multivariate analysis, a poor vaginal/pelvic control rate correlated with age > or =60 years old (relative risk [RR], 3, 95% CI, 1-12; p = 0.01), International Federation of Gynecology and Obstetrics (FIGO) Grade 3 (RR, 9, 95% CI, 2-35; p = 0.03), and LVI (RR, 4, 95% CI, 1-13; p = 0.051). The depth of myometrial invasion and CSS, however, were not significant. With regard to pelvic control specifically, the presence of GOG#99 HR features did not affect the pelvic control rate. The 5-year rate for HR patients was 96% (95% CI, 90-100%) vs. 96% (95% CI, 94-99%) for those without HR disease (p = 0.48). Even when the CSS effect was taken into account, the influence of HR features on pelvic control was still not significant (p = 0.51). In contrast, pelvic control was significantly influenced when patients were grouped according to CSS and stage/grade substages. For those with Stage IB Grade 3-IIB and no CSS, the 5-year pelvic control rate was 86% compared with 97% for those with Stage IB Grade 3-IIB and CSS, 97% for Stage IB, Grade 1-2 without CSS, and 100% for those with Stage IB, Grade 1-2 and CSS (p = 0.027). The 5-year disease-free survival rate was 93% (95% CI, 90-96%). On multivariate analysis, poor disease-free survival correlated with age > or =60 years (RR, 5; 95% CI, 1-18; p = 0.002), FIGO Grade 3 (RR 5, 95% CI 2-17; p = 0.013), and LVI (RR 3, 95% CI 1-8; p = 0.054). Unlike pelvic control, disease-free survival was significantly affected by GOG#99 HR features, with a 5-year rate of 87% (95% CI, 76-99%) vs. 94% (95% CI, 91-97%) for those without HR features (p = 0.027). The 5-year overall and disease-specific survival rate was 93% and 97%, respectively. The overall 5-year actuarial rate of Grade 3 or worse complications was 1% (95% CI, 0-2%). CONCLUSION: Tumor grade, depth of invasion, and the use of CSS were better predictors of pelvic control than the GOG#99 HR factors. IVRT alone seemed to provide adequate tumor control with very low morbidity. Therefore, it seems prudent to consider it for intermediate-risk patients because of its superior therapeutic ratio compared with that for surgery alone or pelvic RT. Additional follow-up, however, with a larger number of patients is needed, especially for those with LVI.     

Ic期子宫内膜癌患者中MPA和EBRT的联合疗效

Objective: To report the comparative effect of combined medroxyprogesterone acetate (MPA) and external beam pelvic radiotherapy (EBRT) with EBRT alone on local or distant recurrences, overall survival and treatment related toxicities in patients with stage Ic grade 3 endometrial cancer. Methods: A retrospective review of 80 International Federation of Gyne-cology and Obstetrics (FIGO) stage Ic grade 3 endometrial carcinoma patients treated between October 1994 and October 2004 at Renmin Hospital, Wuhan University, China was performed. All patients underwent surgery, of which 40 patients in arm I received combined MPA and EBRT while in arm II 40 patients received only adjuvant EBRT after surgery. The median dose of EBRT in arm I was 50 Gy (range 36-54 Gy) and in arm II was 45.2 Gy (range 43.2-50.4 Gy). Multivariate analysis was performed for the prognostic factors and Kaplan-Meier method was used for overall survival. Results: Of the 80 eligible patients, 40 in each group could be evaluated. The follow-up times ranged from 4-98 months with a median of 45 months. The overall survival rates at five years were 73% among patients treated with combined MPA and EBRT and 28.2% among patients treated with EBRT alone (P < 0.001). The rate of distant metastasis was significantly higher among patients treated with EBRT alone group than combined MPA and EBRT (55% vs 25%, P = 0.006) while no difference in loco regional recur-rence rates was observed in both treatment groups. Most of the side effects observed in the combined MPA and EBRT group. Age (P < 0.001) and the presence of progesterone receptors (P = 0.003) were independent significant prognostic factors for overall survival in multiple regression analysis. Conclusion: We has been concluded that the addition of progestagen to external beam pelvic radiotherapy significantly improved survival and reduced distant metastasis among women with stage Ic grade 3 endometrial cancer.     

IUdR polymers for combined continuous low-dose rate and high-dose rate sensitization of experimental human malignant gliomas

Local polymeric delivery enhances IUdR radiosensitization of human malignant gliomas (MG). The combined low-dose rate (LDR) (0.03 Gy/h) and fractionated high-dose rate (HDR) treatments result in cures of experimental MGs. To enhance efficacy, we combined polymeric IUdR delivery, LDR, and HDR for treatments of both subcutaneous and intracranial MGs. In vitro: Cells (U251 MG) were trypsinized and replated in triplicate 1 day prior to LDR irradiation in media either without (control) or with 10 microM IUdR. After 72 hr, LDR irradiation cells were acutely irradiated (1.1 Gy/min) with increasing (0, 1.25, 2.5, 5.0, or 10 Gy) single doses. Implantable IUdR polymers [(poly(bis(p-carboxyphenoxy)-propane) (PCPP): sebaic acid (PCPP:SA), 20:80] (50% loading; 10 mg) were synthesized. In vivo: For flank vs. intracranial tumors, mice had 6 x 10(6) subcutaneous vs. 2 x 10(5) intracranial cells. For intracranial or subcutaneous MGs, mice had intratumoral blank (empty) vs. IUdR polymer treatments. One day after implantation, mice had immediate external LDR (3 cGy/h x 3 days total body irradiation) or HDR (2 Gy BID x 4 days to tumor site) or concurrent treatments. For the in vitro IUdR treatments, LDR resulted in a striking increase in cell-killing when combined with HDR. For the in vivo LDR treatments of flank tumors, the growth delay was greater for the IUdR vs. blank polymer treatments. For the combined LDR and HDR, the IUdR treatments resulted in a dramatic decrease in tumor volumes. On day 60 the log V/V0 were -1.7 +/- 0.22 for combined LDR + HDR + IUdR polymer (P < 0.05 vs. combined LDR + HDR + blank polymer). Survival for the intracranial controls was 22.9 +/- 1.2 days. For the blank polymer + LDR vs. blank polymer + LDR + HDR treatments, survival was 25.3 +/- 1.7 (P = NS) vs. 48.1 +/- 3.5 days (P < 0.05). For IUdR polymer + LDR treatment survival was 27.3 +/- 2.3 days (P = NS). The most striking improvement in survival followed the IUdR polymer + LDR + HDR treatment: 66.0 + 6.4 days (P < 0.05 vs. blank polymer + LDR + HDR). The polymeric IUdR delivery plus combined continuous LDR and HDR treatments results in growth delay and improved survival in animals bearing the MG xenografts. This treatment may hold promise for the treatment of human MGs.     

宫颈癌盆腔淋巴结转移同步推量调强放射治疗的临床研究

目的 子宫颈癌是妇女最常见恶性肿瘤之一,对于中晚期宫颈癌患者放疗是较理想和有效的选择.本研究通过观察不同放疗方法在中晚期宫颈癌合并盆腔淋巴结转移患者的临床应用,比较同步推量调强放射治疗(simultaneous modulated accelerated radiotherapy,SMART)和常规放射治疗(conventional radiotherapy,CRT)对中晚期宫颈癌合并盆腔淋巴结转移患者的剂量学差异和临床效果.方法 选取2009 12-01-2015-06-30临沂市肿瘤医院68例接受SMART和65例行CRT的ⅡB～ⅢB期宫颈癌合并盆腔淋巴结转移患者为研究对象.SMART计划:PTV达到处方剂量50.4～52.2 Gy/28～29次,1.8～1.85 Gy/次,同时给予P-GTV 61.6～67.2 Gy/28～29次,2.2～2.4 Gy/次,计划进行18次给予缩野.CRT计划:5次/周,1.8～1.9 Gy/次,照射剂量达30 Gy后,中间档铅4 cm照射,4次/周,1.8～2.0 Gy/次,至全盆总量达48.2～53.2 Gy;盆腔淋巴结转移侧加量至54.2～58.2 Gy.体外放疗同时给予一体化后装放疗及静脉化疗.比较靶区剂量、危及器官受照射剂量、近期疗效、急慢性不良反应和生存率.结果 两组患者的靶区剂量比较,SMART组中位P-GTV剂量64.7 Gy,CRT组的体外放疗中位剂量(全盆十四野十淋巴结区缩野后)55.4 Gy,两组比较差异有统计学意义,t=33.717,P＜0.001.SMART与拟行CRT计划比较,SMART组小肠(t=12.888,P＜0.001)、结肠(t=11.828,P＜0.001)、膀胱(t=12.135,P＜0.001)、脊髓(t=3.523,P=0.002)、股骨头(t=3.545,P=0.002)受照射剂量明显降低;SMART组的急性消化道反应(x2=9.965,P=0.019)和泌尿系统不良反应(x2=11.092,P=0.011)及骨髓抑制(x2 =9.071,P=0.028)均明显减少,差异均有统计学意义;SMART组的慢性消化道(x2=7.226,P=0.027)和泌尿系统不良反应(x2 =9.344,P=0.025)均明显减少,差异均有统计学意义.SMART与CRT组的CR(87.7％ vs72.1％,P=0.029)及近期有效率(98.5％ vs 86.9％,P=0.012)比较有统计学意义,SMART组明显提高.SMART组总的生存率(P=0.014)及无瘤生存率(P=0.001)均明显提高;1年生存率比较无统计学意义,x2=0.257,P=0.612;3年生存率(x2 =5.399,P=0.020)和5年生存率(x2=5.965,P=0.015)比较差异有统计学意义,SMART组明显提高.结论 SMART比较CRT,对中晚期宫颈癌合并盆腔淋巴结转移患者可获得理想的剂量分布,靶区可获得根治性剂量,邻近危及器官得到保护,急慢性毒副作用明显降低,完全缓解率及无瘤生存率明显提高.     

Concurrent weekly cisplatin plus external beam radiotherapy and high-dose rate brachytherapy for advanced cervical cancer: a control cohort comparison with radiation alone on treatment outcome and complications

PURPOSE: To test, though a control-cohort study, the hypothesis that concurrent chemoradiotherapy (CCRT) using weekly cisplatin, plus high-dose rate intracavitary brachytherapy (HDRICB) is superior to radiation (RT) alone in patients with advanced cervical cancer. METHODS AND MATERIALS: A total of 171 patients with Stage IIB-III cervical cancer were enrolled in this study. Seventy patients were treated with CCRT and the results were compared with those of 101 patients who had been treated with RT using the same protocol at an early period. RT consisted of 45 Gy in 25 fractions to the whole pelvis, followed by a 12.6-Gy boost to the parametrium. Four courses of HDRICB using 6.0 Gy to Point A were performed. Chemotherapy consisted of weekly cisplatin at a dose of 40 mg/m(2) for 5-6 cycles. RESULTS: The 4-year actuarial survival was 74% for the CCRT group and 68% for the RT group (p = 0.60). The 4-year pelvic relapse-free survival was 87% for the CCRT group and 85% for the RT group (p = 0.37). The 4-year distant metastases-free survival was 75% for the CCRT group and 76% for the RT group (p = 0.44). The cumulative incidence of gastrointestinal and genitourinary injuries of grade 3 or above was 14.3% for the CCRT group and 7.9% for the RT group (p = 0.19). CONCLUSION: This study did not show a survival benefit of CCRT with weekly cisplatin and HDRICB for Stage II-III cervical cancer, nor did it demonstrate a significant increase of late complications when comparing with RT alone.     

调强放疗总疗程时间延长对局部晚期鼻咽癌疗效的影响

目的 探讨在调强放疗(IMRT)模式下总疗程时间(OTT)延长对局部晚期鼻咽癌疗效的影响.方法 对2001年5月至2007年4月在本中心首诊接受IMRT的376例T3-4N0-3M0期鼻咽癌患者进行回顾分析.以中位OTT为界分为OTT≤45 d和>45 d两组并比较差异,用Cox回归模型行多因素预后分析,放疗时间与局部控制率关系采用直线回归分析.结果 全组OTT≤45 d和>45 d组鼻咽2年局部控制率相似(94.9%和93.1%;χ2=2.83,P>0.05),T3期患者的也相似(96.3%和98.7%;χ2=2.18,P>0.05),T4期患者的不同(92.2%和83.1%;χ2=6.30,P<0.05).放疗中断发生在治疗开始3周前、3周后或3周前后的2年局部控制率相似(98%、96%或93%;χ2=2.21,P=0.531).放化疗模式下OTT>45 d组比OTT≤45 d组2年局部控制率低(93.1%和97.5%;χ2=4.69,P=0.030).多因素分析显示OTT是T4期患者局部控制率的影响因素.直线回归分析显示T4期患者疗程每延长1 d,2年局部控制率大约下降2.7%.OTT≤45 d和>45 d组的2年无瘤生存率、无远转生存率及总生存率均相似[84.1%和78.7%(χ2=0.02,P=0.881)、87.0%和86.1%(χ2=0.85,P=0.358)、91. 7%和92.2%(χ2=0.06,P=0.806)],T3及T4期患者的均也相似[83.7%和83.2%(χ2=0.07,P=0.798)、86.6%和85.7%(χ2=0.02,P=0.898)、93.7%和94.8%(χ2=0.03,P=0.862)及81.4%和72.3%(χ2=0.16,P=0.687)、82.6%和86.9%(χ2=1.78,P=0.182)、88.3%和87.5%(χ2=0.60,P=0.438)].多因素分析显示T分期、N分期是无瘤生存和总生存的影响因素,N分期是无远转生存率的影响因素.结论 IMRT模式下OTT延长将导致T4期鼻咽癌患者局部控制率降低,临床上应尽量避免疗程延长.     

The American Brachytherapy Society recommendations for high-dose-rate brachytherapy for carcinoma of the cervix

PURPOSE: This report presents guidelines for using high-dose-rate (HDR) brachytherapy in the management of patients with cervical cancer, taking into consideration the current availability of resources in most institutions. METHODS: Members of the American Brachytherapy Society (ABS) with expertise in HDR brachytherapy for cervical cancer performed a literature review, supplemented their clinical experience to formulate guidelines for HDR brachytherapy of cervical cancer. RESULTS: The ABS strongly recommends that definitive irradiation for cervical carcinoma must include brachytherapy as a component. Each institution should follow a consistent treatment policy when performing HDR brachytherapy, including complete documentation of treatment parameters and correlation with clinical outcome, such as pelvic control, survival, and complications. The goals are to treat Point A to at least a total low-dose-rate (LDR) equivalent of 80-85 Gy for early stage disease and 85-90 Gy for advanced stage. The pelvic sidewall dose recommendations are 50-55 Gy for early lesions and 55-65 Gy for advanced ones. The relative doses given by external beam radiation therapy (EBRT) vs. brachytherapy depend upon the initial volume of disease, the ability to displace the bladder and rectum, the degree of tumor regression during pelvic irradiation, and institutional preference. As with LDR brachytherapy, every attempt should be made to keep the bladder and rectal doses below 80 Gy and 75 Gy LDR equivalent doses, respectively. Interstitial brachytherapy should be considered for patients with disease that cannot be optimally encompassed by intracavitary brachytherapy. While recognizing that many efficacious HDR fractionation schedules exist, some suggested dose and fractionation schemes for combining the EBRT with HDR brachytherapy for each stage of disease are presented. These recommendations are intended only as guidelines, and the suggested fractionation schemes have not been thoroughly tested. The responsibility for the medical decisions ultimately rests with the treating radiation oncologist. CONCLUSION: Guidelines are established for HDR brachytherapy for cervical cancer. Practitioners and cooperative groups are encouraged to use these guidelines to formulate their treatment and dose-reporting policies. These guidelines will be modified, as image-based treatment becomes more widely available.     

Adenocarcinoma of the endometrium treated with combined irradiation and surgery: study of 437 patients

PURPOSE: To identify prognostic factors and treatment toxicity in a series of operable endometrial adenocarcinomas. METHODS AND MATERIALS: Between November 1971 and October 1992, 437 patients (pts) with endometrial carcinoma, staged according to the 1988 FIGO staging system (225 Stage IB, 107 Stage IC, 4 Stage IIA, 35 Stage IIB, 30 Stage IIIA, 6 Stage IIIB, and 30 Stage IIIC), underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy without (n = 140) or with (n = 297) pelvic lymph node dissection. The chronology of adjuvant RT was not randomized and depended on the usual practices of the surgical teams. Seventy-nine pts (Group I) received preoperative low-dose-rate uterovaginal brachytherapy (mean dose [MD]: 57 Gy). Three hundred fifty-eight pts (Group II) received postoperative RT. One hundred ninety-six pts received low-dose-rate vaginal brachytherapy alone (MD: 50 Gy). One hundred fifty-eight pts had external beam pelvic RT (MD: 46 Gy) followed by low-dose-rate vaginal brachytherapy (MD: 17 Gy). Four pts had external beam pelvic RT alone (MD: 47 Gy). The mean follow-up from the beginning of treatment was 128 months. RESULTS: The 10-year disease-free survival rate was 86%. From 57 recurrences, only 12 were isolated locoregional recurrences. The independent factors decreasing the probability of disease-free survival were as follows: histologic type (clear-cell carcinoma, p = 0.038), largest histologic tumor diameter >3 cm (p = 0.015), histologic grade (p = 0.008), myometrial invasion > 1/2 (p = 0.005), and 1988 FIGO staging system (p = 9.10(-8)). In Group II, the addition of external beam pelvic RT did not seem to independently improve vaginal or pelvic control. The postoperative complication rate was 7%. The independent factors increasing the risk of postoperative complications were stage FIGO (p = 0.02) and pelvic lymph node dissection (p = 0.011). The 10-year rate for Grade 3 and 4 late radiation complications according to the LENT-SOMA scoring system was 3.1%. External beam pelvic RT independently increased the rate for Grade 3 and 4 late complication (RR: 5.6, p = 0.0096). CONCLUSION: Postoperative external beam pelvic RT increases the risk of late radiation complications. After surgical and histopathologic staging with pelvic lymph node dissection, in subgroup of "intermediate-risk" patients (Stage IA Grade 3, IB-C and II), postoperative vaginal brachytherapy alone is probably sufficient to obtain a good therapeutic index. Results for patients with Stage III tumor are not satisfactory.     

Dose rate correction in medium dose rate brachytherapy for carcinoma cervix.

PURPOSE: To establish the magnitude of brachytherapy dose reduction required for stage IIB and III carcinoma cervix patients treated by external radiation and medium dose rate (MDR) brachytherapy at a dose rate of 220+/-10 cGy/h at point A. MATERIALS AND METHODS: In study-I, at the time of MDR brachytherapy application at a dose rate of 220+/-10 cGy/h at point A, patients received either 3060 cGy, a 12.5% dose reduction (MDR-12.5), or 2450 cGy, a 30% dose reduction (MDR-30), to point A and they were compared to a group of previously treated LDR patients who received 3500 cGy to point A at a dose rate of 55-65 cGy/h. Study-II was a prospective randomized trial and patients received either 2450 cGy, a 30% dose reduction (MDR-II (30)) or 2800 cGy, a 20% dose reduction (MDR-II (20)), at point A. Patients were evaluated for local control of disease and morbidity. RESULTS: In study-I the 5-year actuarial local control rate in the MDR-30 and MDR-12.5 groups was 71.7+/-10% and 70.5+/-10%, respectively, compared to 63.4+/-10% in the LDR group. However, the actuarial morbidity (all grades) in the MDR-12.5 group was 58.5+/-14% as against 34.9+/-9% in the LDR group (P < 0.05). Similarly, the grade III and IV morbidity also in the MDR-12.5 group was 12.5+/-9% as against 5.3+/-5% in the LDR group (P < 0.05). No statistically significant difference in morbidity was seen between the MDR-30 and LDR groups. In study-II the 3-year actuarial local control rate in the MDR-II (30) and MDR-II (20) groups was 66.6+/-10% and 74.8+/-9%, respectively. There was a significant correlation between the rectal BED received and the percentage of patients developing rectal morbidity. Only 10% of patients receiving a rectal BED of (100 < 120) Gy3 developed complication as against 62.5% of those receiving a rectal BED of (140 < 160) Gy3 (chi2 = 46.43; P < 0.001). CONCLUSION: We suggest that at a dose rate of 220+/-10 cGy/h at point A the brachytherapy dose reduction factor should be around 30%, as suggested by radiobiological data, to keep the morbidity as low as possible without compromising the local control rates.     

放射治疗对初诊转移性头颈鳞癌预后的影响

目的 基于美国SEER数据库的资料,评估放疗对初诊转移性头颈鳞癌（HNSCC）患者预后的影响。方法 利用SEER数据库筛选2010—2015年初诊为转移性HNSCC的患者1226例,包括放疗组762例（62.1%）,未放疗组464例（37.9%）。采用Kaplan‐Meier法计算癌症特异性生存（CSS）和总生存（OS）,在全组患者中通过Cox多因素回归和倾向配比评分（PSM）评估放疗对预后的影响。依据多因素分析结果将患者分为低、中和高风险组,并在不同风险组中分析放疗对生存的影响。结果 全组患者中位CSS和OS时间分别为11.0个月和10.0个月;放疗组和未放疗组的中位CSS时间分别为13.0个月和6.0个月,中位OS时间分别为12.0个月和6.0个月。多因素分析显示年龄、原发灶部位、T分期、N分期、转移脏器个数、手术、放疗和化疗是独立的预后影响因素（CSS：P值为0.045、0.021、0.001、0.002、<0.001、<0.001、<0.001、<0.001;OS：P值为0.002、<0.001、0.002、<0.001、<0.001、<0.001、<0.001、<0.001）。PSM配对后,在低、中、高风险组中,放疗和未放疗患者3年CSS分别为：62.5%∶23.5%、22.4%∶15.7%和10.5%∶9.6%（P=0.008、0.001、0.203）;3年OS分别为：58.0%∶20.8%、19.8%∶12.7%和7.0%∶6.1%（P=0.002、0.001、0.166）。结论 放疗显著提高低风险和中风险组患者的CSS和OS,但高风险组患者不能从放疗中生存获益。     

放射治疗对初诊转移性头颈鳞癌预后的影响

目的 基于美国SEER数据库的资料,评估放疗对初诊转移性头颈鳞癌（HNSCC）患者预后的影响。方法 利用SEER数据库筛选2010—2015年初诊为转移性HNSCC的患者1226例,包括放疗组762例（62.1%）,未放疗组464例（37.9%）。采用Kaplan‐Meier法计算癌症特异性生存（CSS）和总生存（OS）,在全组患者中通过Cox多因素回归和倾向配比评分（PSM）评估放疗对预后的影响。依据多因素分析结果将患者分为低、中和高风险组,并在不同风险组中分析放疗对生存的影响。结果 全组患者中位CSS和OS时间分别为11.0个月和10.0个月;放疗组和未放疗组的中位CSS时间分别为13.0个月和6.0个月,中位OS时间分别为12.0个月和6.0个月。多因素分析显示年龄、原发灶部位、T分期、N分期、转移脏器个数、手术、放疗和化疗是独立的预后影响因素（CSS：P值为0.045、0.021、0.001、0.002、<0.001、<0.001、<0.001、<0.001;OS：P值为0.002、<0.001、0.002、<0.001、<0.001、<0.001、<0.001、<0.001）。PSM配对后,在低、中、高风险组中,放疗和未放疗患者3年CSS分别为：62.5%∶23.5%、22.4%∶15.7%和10.5%∶9.6%（P=0.008、0.001、0.203）;3年OS分别为：58.0%∶20.8%、19.8%∶12.7%和7.0%∶6.1%（P=0.002、0.001、0.166）。结论 放疗显著提高低风险和中风险组患者的CSS和OS,但高风险组患者不能从放疗中生存获益。     

基于SEER数据库回顾性分析食管神经内分泌癌的放疗价值

目的:基于SEER(surveillance,epidemiology,and end results)数据库分析放疗对食管神经内分泌癌（esophagus neuroendocrine carcinoma,ENEC）患者预后的影响,为这一罕见病理类型的食管癌患者提供临床决策参考。方法:通过SEER*Stat软件收集2004年至2015年间经病理确诊为原发性ENEC的202例患者资料。应用卡方检验分析放疗与患者各临床病理资料的关系,单因素COX风险回归模型得出影响ENEC患者肿瘤特异性生存（cancer special survival,CSS）和总生存（overall survival,OS）的因素,采用Kaplan-Meier法计算生存率并进行亚组分析。结果:卡方检验提示AJCC分期（P=0.001）、T分期（P=0.000）、远处转移（P=0.001）、手术（P=0.001）、化疗（P=0.000）与放疗均相关。单因素COX分析显示肿瘤部位、AJCC分期、T分期、远处转移、手术、化疗是影响ENEC患者CSS和OS的预后因素（P均<0.05）。放疗组患者的CSS（P=0.000）与OS（P=0.000）均优于未放疗组。Kaplan-Meier生存分析显示放疗组与未放疗组患者1、3、5年CSS分别为49.5% vs 27.8%、23.8%vs 7.9%、21.4% vs 3.0%。放疗组CSS优于未放疗组,差异有统计学意义（P=0.000）。进一步亚组分析显示放疗对肿瘤位于食管下1/3部（P=0.000）、未发生远处转移（P=0.009）、未接受手术（P=0.003）、接受化疗（P=0.000）的ENEC患者具有更好的生存获益。结论:放疗可改善ENEC患者的预后,尤其在下1/3部食管癌、未发生远处转移、未接受手术、接受化疗的患者中。