Treatment of advanced cancer of the cervix with transperineal interstitial irradiation

A pilot study using transperineal interstitial implantation to the parametrium in patients with locally advanced carcinoma of the cervix or with distorted anatomy is presented. Twenty-one consecutive patients (2 cervical stump Stage IB, 3 Stage IIB,15 Stage IIIB, 1 Stage IV,,) received one (12) or two (9) implants following 40–45 Gy whole pelvis external irradiation. In addition 8 patients underwent staging laparotomies concurrently with the first implant procedure. Control of the pelvic tumor was accomplished in 18 of 21 patients (85%) with a mean follow-up of 26 months (range 15 to 48 months). Seven patients (33%) developed long term complications (fistula 3, superficial necrosis of the vagina 1, severe proctitis or cystitis 3). Six of the complications occurred in 8 patients (75 % ) who had radioactive sources placed on the surface of the vaginal obturator as a substitute for the lack of tandem. In contrast, only I in the remaining 13 patients (8%) who did not have obturator sources placed, developed long term complications.     

Carcinoma of the cervix: surgical staging and radiotherapy with 32 MeV betatron

Fifty-six patients with squamous cell carcinoma of the cervix were staged by exploratory laparotomy. Twenty-eight of them received radiotherapy with 32 MeV Betatron and intracavitary radium. Twenty-one patients with Stage IB or IIA had a radical hysterectomy, five had post-operative pelvic irradiation, and two had primary exenteration. An overall 23.2% of patients had metastases in the paraaortic fields. Four patients with paraaortic node disease received extended field irradiation: 4500 rad in 5 weeks to paraaortic nodes. Two of them are alive and disease-free at 5.5 to 6.5 years.     

Para-aortic lymph node irradiation in carcinoma of the cervix after exploratory laparotomy and biopsy-proven positive aortic nodes

From July 1970 to January 1977, 23 patients with previously untreated cancer of the cervix (CA CX), mostly Stage IIIB, were included in this study. The pare-aortic lymph nodes (PALN) were histologically documented to have metastatic disease in all 23 patients. External radiation treatment (RT) was delivered using a Colbalt—60 machine to a spade-shaped field to treat the pelvic cavity and para-aortic area. The majority of the patients received 4000–6000 rad to the pelvic cavity and from 5000–5500 rad to the PALN's by external RT. In addition, intracavitary radium was used in 21 patients. Five patients are alive and free of disease at 115, 110, 90, 73 and 45 months after completion of RT. One survivor had clinical Stage IB, one had Stage IIB, and three had Stage IIIB cervical carcinoma. Two of 15 patients with clinically enlarged and suspicious para-aortic nodes are alive, while 3 of 8 patients with clinically normal appearing nodes survived. Three (60%) of the survivors developed late bowel radiation damage. Eighteen patients died—10 during the first year, 3 during the second year, 2 during the third year, 1 during the fourth year and 2 during the eighth year of the follow-up. Five (27.8%) of the patients who died had developed late bowel radiation damage. Fifteen of the 18 died with disease at an average of 21 months. Three patients died of intercurrent disease. Their average survival was 40 months, double that of patients dying of disease. This report suggests that in cancer of the cervix, radiation therapy can control some PALN metastatic disease, but the risk of complications is rather high. In the absence of better methods of management, this risk of complications is justifiable because the alternative is to leave known disease untreated.     

External irradiation and one radium application for carcinoma of the cervix.

Between August 1968 and May 1976 at the Tufts-New England Medical Center, Boston, Massachusetts, 264 patients with carcinoma of the cervix on intact uteri were treated with external irradiation followed by one radium application. Of these patients, 78 presented with Stage 1,126 with Stage II, 51 with Stage III, and 9 with Stage IV disease. In a majority of patients, external irradiation was given with ⁶⁰Co when AP diameter was less than 17 cm, and with a 46 MeV Brown-Boveri Betatron when AP diameter was greater than 17 cm. A whole pelvic dose of 4000 rad was given for tumors smaller than 5 cm in size and 4500 rad for those larger than 5 cm. A dose was then given to the pelvic wall using 4 cm or 5 cm midline blocks. In Stage I disease, tumors of less than 2 cm received no pelvic wall irradiation and tumors greater than 2 cm and Stage HA patients received 1000 rad to both pelvic walls. In Stage IIB and IIIA disease, a dose of 1000 rad was given to the uninvolved pelvic wall and 1500 rad to the involved site. In Stage IIIB disease, after giving 1500 rad to the involved parametria, an additional 500 rad was given with a reduced field to the area of gross tumor in the parametrium. All patients had one radium application for 72 hr 7–14 days after completion of all external irradiation. There were no pelvic failures in Stage I patients, $\text{8}\text{56}$ in Stage IIA, 10/70 in Stage IIB, and $\text{17}\text{52}$ in Stage III. The 5 year no evidence of disease (NED) actuarial survival was 100% in early Stage III (less than 1 cm), 90% in Stage III (greater than 1 cm), 79% in Stage IIA, 58% in Stage IIB, 42% in Stage III and 23% in Stage IV. There was no difference in survival or complications between patients who had tandem and colpostats and those who had protruding tandem.     

The role of radiation therapy in the management of the patient with IB carcinoma of the cervix

From June 30, 1967, through June 30, 1977, 209 patients were treated with IB lesions; 55 of these patients were classified as having bulky, barrel-shaped tumors greater than 4 cm. These 55 patients had a conservative hysterectomy without pelvic lymphadenectomy after a modified radical radiation therapy course. The remainder of the patients had either definitive radiation therapy or radical surgery. The follow-up of all patients from one to ten years reveals excellent local tumor control with only four pelvic failures in the radiotherapy-surgery group and no local failures in the group treated with radiation therapy alone. The treatment program outlined for the 55 radiation therapy-surgery group is unique in three respects: (1) all patients received a maximum of 3000 rad total pelvic dose, (2) the dose delivered from intracavitary radium was 25 % less than that given in the radiation therapy alone group, and (3) the conservative hysterectomy was carried out immediately after the completion of the radiation therapy.     

Clinical experience of fast neutron therapy for carcinoma of the uterine cervix

Fast neutron therapy for locally advanced or radioresistant malignant tumors was started in November 1975 at the National Institute of Radiological Sciences (NIRS), Chiba, Japan. To evaluate the effectiveness of fast neutron therapy, mixed neutron-photon fractionated irradiation, on squamous cell carcinoma of the uterine cervix, 98 patients with Stage IIIb disease were examined to study the correlation between local control rate and histological types. The local control rate after neutron-mixed beam therapy was 73%, which decreased to 66% with photon irradiation. The five year survival rate was 49% for patients receiving neutron therapy and 49% for those receiving photon therapy. There was no statistical significance between neutron and photon therapy; we then attempted to analyze histological types to check for any gain using neutron therapy. This study was a nonrandomized trial. The preliminary results however, gave us useful information for the next of neutron therapy.     

铱~(192)高剂量率后装加外照射治疗宫颈癌105例分析

目的　研究铱192 高剂量率后装加外照射治疗宫颈癌的疗效 ,并发症等。方法　前瞻性治疗 ,全盆腔外照射DT 2 5～ 3 0Gy/3周后 ,再行腔内铱192 后装治疗和盆腔四野垂直照射 :腔内每周 1次 ,A点剂量每次 5～ 7Gy ,总剂量3 0～ 3 5Gy ,盆腔四野照射 ,宫旁剂量 15～ 2 0Gy/1.5～ 2周。 结果　CR PR 10 0 % ,3年生存率Ⅱ期 89.5 % ,Ⅲ期 80 .4% ,全组 83 .8%。结论　本疗法疗效可靠 ,放射性直肠炎、膀胱炎发生率与传统方法相似 ,放射性阴道损伤略高 ,放疗中、放疗后坚持阴道冲洗非常重要。     

Postoperative irradiation in carcinoma of the prostate

Twenty-eight patients received postoperative radiotherapy with curative intent following either radical prostatectomy (18 patients) or enucleative prostatectomy (10 patients). In patients undergoing radical prostatectomy, the indications for postoperative radiotherapy included positive margins in 13, “close” margins in 2, and seminal vesicle involvement in 3 patients. The majority of patients (82%) received total dose to the prostaatc bed in excess of 6500 rad. In over 80% of the patients, the pelvic lymphatics are also treated (to a total dose of 4000–5000 rad). Minimum follow-up is one year, maximum is 10 years, average 54 months, median 41 months. Local recurrence was observed in only 1 patient, who was treated post-enucleativn. All of the patients irradiated after radical prostatectomy clinically remained disease-free locally. Approximately one-half of the patients in both the enucleativn and radial prostatectomy groups developed evidence of distant metastases. The complications of treatment have been comparable to those in patients treated with radiotherapy only. The continence status has not been affected significantly. All patients (5 in the radical prostatectomy group and 2 in the enuclentivn group) with incontinence following completion of radiotherapy had documented impairment of continence prior to radiotherapy. Postoperative radiotherapy administered following either radical or enucleative prostatectomy was tolerated well and resulted in excellent local control.     

Long-term outcome after radiotherapy for FIGO stage IIIB and IVA carcinoma of the cervix

PURPOSE: To report the long-term outcome after radiotherapy with curative intent for Stage IIIB and IVA carcinoma of the cervix. METHODS AND MATERIALS: We retrospectively reviewed 91 patients treated with radiotherapy with curative intent at the University of Florida between January 1980 and December 2003 for Stage IIIB (84 patients) or IVA (7 patients) carcinoma of the cervix. RESULTS: The median follow-up of the surviving patients was 8.8 years. The 5- and 10-year estimates of local control, regional control, locoregional control, relapse-free survival, and overall survival were 53% and 53%, 55% and 47%, 34% and 29%, 30% and 26%, and 29% and 21%, respectively. Ninety percent of the recurrences occurred within 2 years of treatment. Of these, 60% of all failures were local, 29% were regional, and 11% were distant failures alone. Also, 17% of the failures were in the paraaortic nodes with no evidence of failure in the pelvis. Univariate and multivariate analyses were conducted with the endpoint of relapse-free or overall survival. No factor was statistically significant. Complications from therapy were scored using the Radiation Therapy Oncology Group grading system; the overall severe late complication rate was 13% (Grade 3-5). CONCLUSION: This series is one of the most mature of published reports. With long-term follow-up, approximately one-third of patients with Stage IIIB or IVA carcinoma of the cervix were cured, with a 13% complication rate.     

National audit of the management and outcome of carcinoma of the cervix treated with radiotherapy in 1993

The aim of the study was to investigate the UK prevalence of late, severe side-effects associated with radical radiotherapy for cancer of the cervix and try to identify associated factors. All patients treated for cancer of the cervix with radical radiotherapy in 1993 were identified and retrospective case notes studied to determine mortality and severe complications occurring following treatment. Of the 55 radiotherapy departments in the UK that were treating gynaecological malignancy in 1993, 53 participated in the study. There were 1558 patients with carcinoma of the cervix receiving radical radiotherapy as part of their treatment regimen in 1993, whose patterns of treatment were assessed. The main outcome measures were the development of late severe complications as defined by the Franco-Italian Glossary and mortality. Of the patients receiving surgery and radiotherapy, 58.5% underwent Wertheim's procedure. The crude rate of late severe complications in all patients with cervical cancer treated with radical radiotherapy in 1993 was 6.1% (actuarial rate 8%) at 5 years, and only four of the 91 patients who developed complications died as a result of their morbidity. There was no significant correlation of stage, centre size, surgery or radiotherapeutic approach with late morbidity in univariate analysis. The overall survival at 5 years was 47% and was lower than that of the European data from FIGO's 1990–92 cohort, for all stages. Increasing FIGO stage was the only factor significantly associated with mortality. The absence of variables that were significantly associated with late complications may well be related to the relatively low event rate compared to the sample size. Differences in surgical treatment prior to radiotherapy and radiation technique may be confounding the comparison of outcomes. The relatively poor survival for locally advanced disease and the difficulty with which these data were collated indicates that national prospective data collection is urgently required to monitor performance and hence derive best practice.     

Concurrent mitomycin C, 5-fluorouracil,and radiotherapy in the treatment of locally advanced carcinoma of the cervix: a randomized trial

PURPOSE: This is a prospective, Phase III multicenter randomized trial to assess the effectiveness of concurrent intravenous mitomycin C, oral 5-fluorouracil (5-FU), and radiotherapy (RT) in locally advanced carcinoma of the cervix. METHODS AND MATERIALS: Between January 1988 and November 1994, 926 patients with locally advanced carcinoma of the cervix, FIGO Stage IIB-IVA, were entered into this study. The patients were randomized into four arms, as follows: Arm 1: conventional RT; Arm 2: conventional RT and adjuvant chemotherapy; Arm 3: conventional RT plus concurrent chemotherapy; Arm 4: conventional RT plus concurrent chemotherapy and adjuvant chemotherapy. Concurrent chemotherapy consisting of intravenous mitomycin C at 10 mg/m(2) was given on Days 1 and 29, and oral 5-FU at 300 mg/day was administered on Days 1-14 and 29-42 during RT. Adjuvant chemotherapy of 5-FU orally at 200 mg/day was given for three courses of 4 weeks, with a 2-week rest every 6 weeks. Six centers participated in the trial. RESULTS: The median follow-up time was 89 months. Acute side effects were generally higher in concurrent arms, but most of the patients tolerated the treatment well. Bone marrow toxicity was also higher in concurrent arms. The 5-year actuarial disease-free survival (DFS) was 48.2%, 54.1%, 64.5%, and 59.7% for arms 1, 2, 3, and 4, respectively. The pattern of failure revealed a significant increase in locoregional recurrence in the nonconcurrent chemoradiotherapy arm. The local recurrence was 25.5%, 20.6%, 14.3%, and 17.6% for arms 1, 2, 3, and 4, respectively. The metastatic rates were not significantly different in all four arms. At the time of analysis, there were no increases in late side effects, especially in gastrointestinal and genitourinary systems. CONCLUSIONS: Concurrent chemotherapy, mitomycin C, and 5-FU together with conventional RT showed an improved DFS rate when compared with conventional RT alone in patients with locally advanced carcinoma of the cervix.     

The impact of lymph node status on survival in cervical carcinoma

Four hundred and sixty three patients with Stage IB through IIIB primary squamous cell carcinoma of the cervix were treated at the M.D. Anderson Hospital and Tumor Institute between 1968 and 1971. Lymphangiography was performed in 215 patients with tumors in Stages III to IIIB. Data on these 215 patients were reviewed and survival was correlated with lymphangiogram (LAG) status, tumor volume (stage) and selected patient characteristics. Three risk categories were identified using clinical staging and LAG criteria. These risk categories differed in median survival as follows: good risk (Stage IIA and B, LAG negative - 92+ months); intermediate risk (Stage 1111, LAG positive, Stage IIIA and B, LAG negative - 31 months) and poor risk (Stage IIIA and B, LAG positive - 11 months). Frequency of persistent disease and two year failure rates were both positively correlated with stage among LAG negative and LAG positive patients.     

三维适形放疗联合力扑素周化疗治疗宫颈癌腹主动脉旁淋巴结转移的临床研究

目的探讨三维适形放射治疗联合力扑素（LPS）周化疗对宫颈癌腹主动脉旁淋巴结转移的短期疗效和不良反应。方法 64例宫颈癌腹主动脉旁淋巴结转移患者分为单纯放疗组和联合治疗组,每组各32例,两组患者均给予适形放疗,20 Gy/f,每周5次,腹主动脉旁总剂量60 Gy。联合治疗组在三维适形放疗的同时,行力扑素周化疗,每周60 mg/m2,连续3周为1个周期,2个周期后间隔1周。观察临床效果和不良反应。结果单纯放疗组的总有效率为56.3%,临床控制率为81.3%;联合治疗组的总有效率为81.3%,临床控制率为93.8%。两组总有效率差异有统计学意义（P〈0.05）。联合治疗组患者白细胞减少的发生率高于单纯放疗组（P〈0.05）,血小板减少、过敏反应和感觉异常等不良反应发生率差异无统计学意义（P〉0.05）。结论三维适形放疗联合力扑素周化疗能够显著增强宫颈癌腹主动脉旁淋巴结转移的近期疗效,除白细胞减少,其他不良反应未见明显增加。     

Radium implant to the parametrium in the treatment of stage IIIB carcinoma of the cervix: Analysis of dosimetry

Radium needle implant to the parametrium in order to supplement the dose rates to the cervix, parametrium and pelvic wall from a protruding intrauterine tandem was simulated using the skeleton of an adult pelvis in a water phantom. The results of direct dosimetry are presented. The parametrial implant approach was instituted in our clinic in 1975 to minimize local failures, especially parametrial, in Stage IIIB carcinoma of the cervix. The technique is used with patients who cannot accomodate two vaginal ovoids with the intrauterine tandem for conventional intracavitary radium therapy because of the extent of the neoplastic disease. Our dosimetric results showed an increase in the parametrial and pelvic wall dose rates of better than 60% with a typical implant of six half-intensity (0.33 mg/cm.) needles to the affected parametrium; the bladder and rectum dose rates increased by less than 17%. There was a relatively minimal (8–13%) increase in the dose rates to other pelvic node-bearing sites. Results for a minimal implant to both proximal parametria and a clinical example of the parametrial implant application are also presented.     

High-dose-rate afterloading brachytherapy in carcinoma of the cervix: an experience of 1992 patients

Purpose: To report the results of radiation therapy in carcinoma of the cervix treated by external irradiation and high-dose-rate (HDR) intracavitary brachytherapy.

Methods and Materials: This is a retrospective analysis of 2063 patients with histologically proven carcinoma of the cervix treated by external irradiation and HDR intracavitary brachytherapy between March 1985–December 1991. The Kaplan-Meier method was used for survival and disease-free survival analysis. Late complications in the bowel and bladder were calculated actuarially.

Results: There were 71 patients who did not complete the course of irradiation so only 1992 patients were retrospectively analyzed for survival. There were 2 patients (0.1%) in Stage IA, 211 (10.2%) Stage IB, 225 (10.9%) in Stage IIA, 902 (43.7%) in Stage IIB, 14 (0.7%) in Stage IIIA, 675 (32.7%) in Stage IIIB, 16 (0.8%) in Stage IVA, and 16 (0.8%) in Stage IVB. The median follow-up time was 96 months. The actuarial 5-year disease-free survival rate was 79.5%, 70.0%, 59.4%, 46.1%, 32.3%, 7.8%, and 23.1% for Stage IB, IIA, IIB, IIIA, IIIB, IVA, and IVB respectively. The actuarial 5-year disease-free survival rate for Stage IB₁ and IB₂ squamous cell carcinoma was 88.7% and 67.0%. The actuarial 5-year overall survival rate was 86.3%, 81.1%, 73.0%, 50.3%, 47.8%, 7.8%, and 30.8% for Stage IB, IIA, IIB, IIIA, IIIB, IVA, and IVB respectively. Pattern of failure revealed 20.8% local recurrence, 18.7% distant metastases, and 4% in both. The late complication rate Grade 3 and 4 (RTOG) for bowel and bladder combined was 7.0% with 1.9% Grade 4.

Conclusion: HDR brachytherapy used in this series produced pelvic control and survival rates comparable to other LDR series.     

Treatment of cervical carcinoma by total hysterectomy and postoperative external irradiation

The survival rates of 36 patients with early cervical carcinoma who had undergone total hysterectomy and bilateral salpingoophorectomy (THBSO) were compared to the survival rates of 41 patients who were subjected to the radical operation. As an integral part of their therapy both groups postoperatively received adequate doses of external beam supervoltage irradiation. Satisfactory results were obtained in both groups of patients. According to these results THBSO followed by postoperative radiotherapy is adequate treatment for early cervical carcinoma. In comparison to the radical operation or curietherapy alone this type of treatment has the advantage of requiring less surgical or radiotherapeutic expertise; it probably is associated with less morbidity.     

Prognostic value of paraaortic lymph node metastases in patients with ductal adenocarcinoma of the pancreatic head

IntroductionThe role of paraaortic lymphadenectomy for cancer of the pancreatic head is controversial. The aim of this study is to analyze the prognostic role of paraaortic lymph node (PALN) metastases after resection for ductal adenocarcinoma of the pancreatic head.Materials and methodsA retrospective analysis of all patients, who underwent upfront resection for ductal adenocarcinoma of the pancreatic head at the Frankfurt University Hospital from 2011 to 2020 was performed. The primary endpoint was survival, according to the presence of PALN metastases.ResultsOut of 468 patients with pancreatic resection, 148 had an upfront resection for ductal adenocarcinoma. Of those, in 125 (85%) a paraaortic lymphadenectomy was performed. In 19 (15.2%) PALN metastases were detected. The estimated overall median survival after resection was 21.7 months (95% CI 18.8 to 26.4), the disease free survival 16 months (95% CI 12 to 18). Among the patients with lymph node metastases, PALN metastases had no significant influence on overall (18.9 versus 19 months, HR = 1.3, 95% CI 0.7 to 2.6, p = 0.392) or disease free survival (14 versus 10.7 months, HR = 1.7, 95% CI 0.9 to 3.2, p = 0.076). After adjusting for T-stage, N-stage, grade, resection margin, PALN metastases, and adjuvant therapy, only adjuvant therapy had a prognostic significance for overall survival (HR = 0.47, 95% CI 0.26 to 0.85, p = 0.013).ConclusionPatients with ductal adenocarcinoma of the pancreatic head and PALN metastases do not have inferior outcomes than those with regional lymph node metastases. Thus, positive PALN should not be considered a contraindication for resection.     

The prediction of late rectal complications in patients treated with high dose-rate brachytherapy for carcinoma of the cervix

: The aim of this work is to invetigate an unusually high rate of late rectal complications in a group of 43 patients treated with concomitant irradiation and chemotherapy for carcinoma of the cervix between December 1988 and April 1991, with a view to identifying predictive factors.

: The biologically effective dose received by each patient to the rectal reference point defined by the International Commission of Radiation Units and Measurements, Report 38, were calculated. Radiotherapy consisted of 46 Gy external beam irradiation plus three dose-rate intracavitary treatments of 10 Gy each prescribed to point A. Cisplatin 30 mg/m² was given weekly throughout the duration of the irradiation. The results have been compared to data from 119 patients treated with irradiation alone to assess the cofounding effect of the cisplatin.

: The relationship between the biologically effective dose delivered to the rectal reference point and the development of late complications shows a strong dose-response with a threshold for complications occurring at aproximately the same biologically effective dose threshold as that found for external beam irradiation in the head and neck region. The date from the group of patients treated wihout cisplatin is comparable to the date from the first group of patients in the lower dose ranges; the higher doses were not used and thus are not available for comparison.

: Using the linear quadratic model applied to our clinical results, we have established a threshold for late rectal complications for patients treated with external beam irradiation and high dose-rate brachytherapy for carcinoma of the cervix. This threshold is consistent with similar data for external irradiation in the head and neck region.