Treatment Of Uterine Cervix Cancer Research Articles

Hypofractionated versus standard chemoradiotherapy in the definitive treatment of uterine cervix cancer: interim results of a randomized controlled clinical trial

PurposeConcurrent chemoradiation has been the mainstay of treatment for cervix cancer. We aimed to evaluate the non-inferiority of hypofractionated chemoradiation.MethodsThis study was designed as a phase 2, 1:1 randomized, investigator-blinded, controlled, non-inferiority trial and we report the interim results after 50% accrual. Cervical cancer patients with FIGO stages IIA–IIIC were recruited from April 2021 to September 2022. The intervention consisted of 40 Gy of 3D-conformal radiation therapy (RT) in 15 fractions over 3 weeks. In the control group, patients received standard chemoradiation of 45 Gy in 25 fractions over 5 weeks. Both groups received concurrent weekly cisplatin (40 mg/m2). Intravaginal brachytherapy of 28 Gy in 4 weekly fractions was delivered starting 1 week after the end of chemoradiation. The primary outcome was complete clinical response(CCR) at 3 months. Secondary outcomes included acute gastrointestinal (GI), genitourinary(GU), skin, and hematologic toxicities. A p value less than 0.05 was considered significant for analyses.Results59 patients were randomized; 30 in the control group and 29 in the intervention group. 20/30 (66.7%) of the patients in the control group and 19/29 (65.5%) in the intervention group achieved a CCR (absolute difference of 0.011, 95% CI − 0.23 to 0.25, p value: 0.13). There was a significantly higher rate of acute grade ≥ 3 GI toxicity in the intervention group (27.6%) compared with the control group (6.7%) (p value 0.032).ConclusionsDespite an absolute difference of 1.1% in the 3-month CCR, our interim analysis failed to show the non-inferiority of the hypofractionated chemoradiation. Due to the higher GI toxicities, we will continue this trial using intensity-modulated radiation therapy.Registration number and dateClinicalTrials.gov: NCT04831437, 2021.4.1.

History of radiotherapy in the treatment of uterine cervix cancer: an overview.

History of radiotherapy in the treatment of uterine cervix cancer: an overview.

Leveraging National Cancer Institute Programmatic Collaboration for Uterine Cervix Cancer Patient Accrual in Puerto Rico.

Women in the U.S. Commonwealth of Puerto Rico (PR) have a higher age-adjusted incidence rate for uterine cervix cancer than the U.S. mainland as well as substantial access and economic barriers to cancer care. The National Cancer Institute (NCI) funds a Minority/Underserved NCI Community Oncology Research Program in PR (PRNCORP) as part of a national network of community-based health-care systems to conduct multisite cancer clinical trials in diverse populations. Participation by the PRNCORP in NCI’s uterine cervix cancer clinical trials, however, has remained limited. This study reports on the findings of an NCI site visit in PR to assess barriers impeding site activation and accrual to its sponsored gynecologic cancer clinical trials. Qualitative, semi-structured individual, and group interviews were conducted at six PRNCORP-affiliated locations to ascertain: long-term trial accrual objectives; key stakeholders in PR that address uterine cervix cancer care; key challenges or barriers to activating and to enrolling patients in NCI uterine cervix cancer treatment trials; and resources, policies, or procedures in place or needed on the island to support NCI-sponsored clinical trials. An NCI-sponsored uterine cervix cancer radiation–chemotherapy intervention clinical trial (NCT02466971), already activated on the island, served as a test case to identify relevant patient accrual and site barriers. The site visit identified five key barriers to accrual: (1) lack of central personnel to coordinate referrals for treatment plans, medical tests, and medical imaging across the island’s clinical trial access points; (2) patient insurance coverage; (3) lack of a coordinated brachytherapy schedule at San Juan-centric service providers; (4) limited credentialed radiotherapy machines island-wide; and (5) too few radiology medical physicists tasked to credential trial-specified positron emission tomography scanners island-wide. PR offers a unique opportunity to study overarching and tactical strategies for improving accrual to NCI-sponsored gynecologic cancer clinical trials. Interview findings support adding and re-tasking personnel for coordinated trial-eligible patient referral, accrual, and treatment.

Uterine cervix cancer treatment at Radiumhemmet: 90 years' experience. Time trends of age, stage, and histopathology distribution

Since the introduction of screening programs for cervical cancer (CC) the incidence has decreased and CC is discovered at an earlier stage. The purpose of this study was to analyze time trends in age, stage, and histopathology over a 90-year period and to our knowledge this is the largest single institutional series in the literature of invasive cervical carcinoma (CC) cases. This is a retrospective study comprising 18,472 women treated for CC from 1914 until 2004 at Radiumhemmet, Stockholm. The material is part of the international CC statistics published since 1937 in the League of Nations' Annual Reports, and since 1958 under the patronage of International Federation of Gynecology and Obstetrics (FIGO). During the 90-year study period, the annual number of cases treated increased to over 400 up until 1965, after which there was a gradual drop to less than 100 cases in 2004. A pronounced shift toward earlier stages at diagnosis was noted. The mean age at diagnosis increased in all stages, predominantly in advanced stages. A reduction in squamous cell carcinoma (SCC) cases and a sixfold increase in the proportion of adenocarcinoma (AC) cases were observed. The mean age at diagnosis for squamous and AC cases shifted after 1970, when the SCC cases ultimately became 3 years older than the AC cases in contrast to around 1950 when they were 3 years younger than the AC cases. The changes in the distribution by age, stage, and histopathology during this 90-year period are probably associated with: improved social conditions and increased access to health care, the introduction of screening programs for CC in the 1960s, and a change in the risk factors for CC (changed sexual behavior, introduction of contraceptive pills, and changed smoking habits).This is a study on changes in the distribution by age, stage, and histopathology in a large series of cervical cancer treated in Sweden during a 90-year period. It also includes an historical review about the development of staging rules and the international reporting system for gynecological cancers.

Definitive radiotherapy for uterine cervix cancer: long term results for patients treated in the period from 1998 till 2002 at the Institute of Oncology Ljubljana

BackgroundThe aim of this retrospective study was to analyse results of the two-dimensional (2D) uterine cervix cancer treatment at the Institute of Oncology Ljubljana from 1998 till 2002, before the three-dimensional (3D) approach was introduced in our clinical practice.MethodsNinety-eight patients with the following FIGO stage distribution were analysed: 10% IB, 7% IIA, 37% IIB, 4% IIIA and 42% IIIB. The influence of age, haemoglobin level, histology, grade, stage, lymph node status, cumulative point A dose, and an overall treatment time on the survival and local control (LC) were evaluated. Acute and late side effects were assessed.ResultsFive and 8-year overall survival (OS), disease specific survival (DSS) and LC rate were as follows: 47.2% and 43.0%, 54.7% and 53.4%, 74.9% and 72.5%, respectively. Point A dose and histology of the tumour influenced OS, positive lymph nodes DSS and point A dose LC rate. Probability of grade three and four late complications in the first five years was 7.1% for gastrointestinal tract and 3.3% for genitourinary system and vagina.ConclusionsPoint A dose was independent predictor of OS and LC rate, lymph node status predicted DSS, while histology of the tumour influenced OS.

P2-053 - A Case of Squamous Cell Carcinoma of Anal Canal Occurring 10 Years after Hysterectomy for Uterine Cervical Cancer

ABSTRACT Anal cancer is rare tumor, accounting for ∼1% of colorectal malignancy in Japan. We report metachronous anal cancer occurred after the treatment of uterine cervix cancer. A 36-year-old woman was referred to our hospital complaining of left supraclavicular node swelling and protruding mass at anus. She had a history of hysterectomy 10 years ago due to early staged uterine cervix cancer (carcinoma in situ) at another hospital. PET-CT and colonoscopy showed apparent tumor from anus to lower rectum (Rb) and multiple hypermetabolic lesions at paraaortic lymph nodes and left supraclavicular lymph node. Interestingly, there were no lesions seen in inguinal lymph nodes. Endoscopic biopsy of anus and fine needle aspiration of her cervical lymph node was positive for squamous carcinoma. After four cycles of the combination chemotherapy with 5-FU and cisplatin (FP), colonoscopy showed a remarkable shrinkage of primary mass but residual tumor at anus. Subsequent PET-CT showed disappearance hypermetabolic uptakes except at anus; therefore, she received additional two cycles of the chemotherapy with concurrent radiotherapy to the pelvis (60 Gy of RT with two cycles of FP). Both of uterine cervical cancer and anal cancer have been discussed in terms of HPV infection. Our experience with the present case suggests that it is necessary to take anal canal cancer as a metachronous cancer into consideration in the course of observations after the treatment of uterine cervical cancer.

SU‐E‐T‐515: Comparison of Two Dose‐Specification Methods for the Treatment of Uterine Cervix Cancer with HDR Brachytherapy Using a Tandem and Ring Applicator

To compare the dose to the high-risk clinical target volume (HRCTV)-D90 and dose-limiting structures with the dose prescription to point A (Manchester system) using conventional methods to image-guided treatment planning with dose optimization and a dose prescription to D90 of the HRCTV. CT-MR-fused image sets for 16 patients (stage IA2-IIIB) with uterine cervix cancer were obtained for each of 5 fractions of HDR brachytherapy using tandem and ring applicators to generate 2 sets of plans. In the first set, the dose was prescribed to point A with a standard dwell weight pattern reflecting the Manchester system loading pattern. In the second set, the dose was prescribed to D90 of the HRCTV with graphical plan optimization. Parameters of clinical significance (HRCTV-D90 and dose received by 1.0, 2.0, and 5.0cc of the bladder, rectum, and sigmoid) were compared, as recommended by GEC-ESTRO. HRCTV-V for 6 patients was =30cc (largest radius, <2.0cm) and >30cc (largest radius, =2cm) for the others. For the first set of plans, when HRCTV-V was <30cc, the ratio of doses HRCTV-D90/dose to point A varied from 1.10 to 1.40. When HRCTV-V was >30cc, it varied from 0.75 to 0.95. In the second set of plans, HRCTV-D90 always received the prescription dose. Doses to 2cc of one or more organs at risk exceeded >10% of the limiting doses for 9 patients in the first set of plans but remained <10% in all patients in the second set of plans. A 10-25% dose reduction to 2cc of the bladder and 15-35% to 2cc of the rectum and sigmoid occurred in the second set of plans. Image-guided brachytherapy with dose optimization yields a prescribed dose to the HRCTV-D90 while maintaining doses to organs at risk close to their limiting value, offering a dosimetric benefit over the traditional method.

Estimation of Homeostatic Activity of the Human Body and Its Systems in Treatment of Uterine Cervix Cancer

Changes in homeostatic parameters of the human body and its systems caused by chemotherapy and radiation therapy can be assessed by complex monitoring of peripheral blood parameters (AKS-ENOFIT system). Such monitoring shows changes in the dynamic curves of patient body state and their dependence on radiation dose. In contrast to radiation therapy, the zigzag shape of these curves becomes more pronounced at lower radiation doses. This is due to the homeostasis phenomenon and can be regarded as evidence of regulation of homeostasis.

Evaluation of toxicity of surgery and/or chemoirradiation treatment of uterine cervix cancer

To evaluate acute and chronic toxicity of chemoirradiation treatment (neoadjuvant, adjuvant and radical treatment) in patients diagnosed with cervix cancer. From December 1999 to August 2007, 53 patients diagnosed with adenocarcinoma or squamous cell carcinoma of the uterine cervix received neoadjuvant, adjuvant or radical chemoirradiation. Acute gastrointestinal toxicity of grade 3 or more in 9 patients (17%) and haematological toxicity of grade 3 or more in 9 patients (17%). Chronic toxicity of grade 3 or more was shown in only 2 patients (4%). The most frequent toxicities were gastrointestinal toxicity and haematological toxicity. The most frequent chronic toxicities were gastrointestinal toxicity and vaginal toxicity. We report that the combined neoadjuvant, adjuvant or radical chemoirradiation treatment with weekly cisplatin chemotherapy (40 mg/m(2)/week) in patients diagnosed with cervix cancer is a well tolerated treatment and chronic and acute toxicity is low-grade. This treatment scheme has easy compliance.

Comparison of low and high dose rate brachytherapy in the treatment of uterine cervix cancer. Retrospective analysis of two sequential series

This retrospective analysis aims to report on the comparative outcome of cervical cancer patients treated with low dose rate (LDR) and high dose rate (HDR) brachytherapy. From 1989 to 1995, 190 patients were treated with low dose rate (LDR) brachytherapy (LDR group) and from 1994 to 2001, 118 patients were treated with high dose rate (HDR) brachytherapy (HDR group). FIGO stage distribution for the LDR group was Stage I: 6.3%; Stage II: 57.4%; and Stage III: 36.3% and for the HDR group Stage I: 9.3%; Stage II: 43.2%; and Stage III: 47.4%. All patients were treated with telecobalt external-beam radiotherapy (EBR). Median doses of LDR brachytherapy at Point A were 40 Gy and 50 Gy for patients treated with 1 and 2 implants, respectively. All patients from the HDR group were treated with 24 Gy in 4 fractions of 6 Gy to Point A. Survival, disease-free survival, local control, and late complications at 5 years, were endpoints compared for both groups. Median follow-up time for LDR and HDR groups was 70 months (range, 8-127 months) and 33 months (range, 4-117 months), respectively. For all stages combined, overall survival, disease-free survival, and local control at 5 years were better in the LDR group (69% vs. 55%, p = 0.007; 73% vs. 56%, p = 0.002; and 74% vs. 65%; p = 0.04, respectively). For clinical Stages I and II, no differences was seen in overall survival, disease-free survival, and local control at 5 years between the two groups. For clinical Stage III, overall survival and disease-free survival at 5 years were better in the LDR group than in the HDR group (46% vs. 36%, p = 0.04 and 49% vs. 37%, p = 0.03, respectively), and local control was marginally higher in the LDR group than in the HDR group (58% vs. 50%, p = 0.19). The 5-year probability of rectal complications was higher in the LDR group than in the HDR group (16% vs. 8%, p = 0.03) and 5-year probability of small bowel and urinary complications was not statistically different between the the LDR group and the HDR group (4.6% vs. 8.9%, p = 0.17 and 6% vs. 3%, p = 0.13, respectively). This comparative series suggests similar outcome for Stages I and II patients treated with either HDR or LDR brachytherapy. Lower overall and disease-free survival and marginally lower local control were observed for Stage III patients treated with HDR brachytherapy. Less late rectal complications were observed in the HDR group patients. These findings were probably the result of the relatively low HDR brachytherapy dose delivered at Point A.

Radiotherapy alone in the treatment of uterine cervix cancer with telecobalt and low-dose-rate brachytherapy: retrospective analysis of results and variables

Purpose: This retrospective analysis aims to report results and variables from patients with cervix cancer treated by radiation therapy alone with telecobalt and low-dose-rate brachytherapy (LDRB). Methods and Materials: Between September 1989 and September 1995, 190 patients with histologic diagnosis of cervix carcinoma were treated with telecobalt for external beam radiotherapy (EBR), followed by one or two insertions of LDRB. Stage distribution according to patients was the following: IB, 12; IIA, 4; IIB, 105; and IIIB, 69. Median dose of EBR at whole pelvis was 40 Gy, and median parametrial doses for Stages II and III patients were 50 Gy and 60 Gy, respectively. Median doses of LDRB at point A for patients treated with one and two insertions were 38 Gy and 50 Gy, respectively. Results: Median follow-up time was 70 months (range: 8–127 months). Overall survival, disease-free survival, and 5-year local control of patients at Stages I, II, and III were 83%, 78%, and 46%; 83%, 82%, and 49%; and 92%, 87%, and 58%, respectively. Overall incidence of late complications in the rectum, small bowel, and urinary tract was 15.3% (19/190), 4.2% (8/190), and 6.8% (13/190), respectively. The actuarial 5-year rectal, small bowel, and urinary incidence of late complications was 16.1%, 4.6%, and 7.6%, respectively. Clinical stage was the only significant variable for overall 5-year survival ( p = 0.001), for disease-free survival ( p = 0.001), and for local control ( p = 0.001). Stage II patients more than 50 years old had better disease-free survival and local control at 5 years ( p = 0.004). None of the analyzed variables influenced the actuarial 5-year incidence of late complications. Conclusions: Results of this series suggest that the use of telecobalt equipment for EBR with doses up to 50 Gy at whole pelvis, prior to brachytherapy, is an acceptable technique for radiation therapy alone in the treatment of cervix cancer, especially in developing countries, including Brazil, where telecobalt machines still prevail.

Concurrent chemoradiotherapy in cervical cancer (a new paradigm in cervical cancer treatment).

During the last century, the mainstay for the treatment of uterine cervix cancer has been via two main primary treatment modalities, these being radical surgery (radical hysterectomy and regional lymph nodes dissection) and radiotherapy. Generally, radical surgery is restricted to stages I and IIa of FIGO (the International Federation of Gynecology and Obstetrics) Classification, while radiotherapy may be applied to all stages of cervical cancer. In 1999 the National Cancer Institute Clinical Announcement established concurrent chemoradiotherapy as a new primary treatment modality, which is the focus of this review.

High-dose-rate brachytherapy in the treatment of uterine cervix cancer. Analysis of dose effectiveness and late complications

Purpose: This retrospective analysis aims to report results of patients with cervix cancer treated by external beam radiotherapy (EBR) and high-dose-rate (HDR) brachytherapy. Methods and Materials: From September 1992 to December 1996, 138 patients with FIGO Stages II and III and mean age of 56 years were treated. Median EBR to the whole pelvis was 45 Gy in 25 fractions. Parametrial boost was performed in 93% of patients, with a median dose of 14.4 Gy. Brachytherapy with HDR was performed during EBR or following its completion with a dose of 24 Gy in four weekly fractions of 6 Gy to point A. Median overall treatment time was of 60 days. Patient age, tumor stage, and overall treatment time were variables analyzed for survival and local control. Cumulative biologic effective dose (BED) at rectal and bladder reference points were correlated with late complications in these organs and dose of EBR at parametrium was correlated with small bowel complications. Results: Median follow-up time was 38 months. Overall survival, disease-free survival, and local control at 5 years was 53.7%, 52.7%, and 62%, respectively. By multivariate and univariate analysis, overall treatment time up to 50 days was the only statistically significant adverse variable for overall survival ( p = 0.003) and actuarial local control ( p = 0.008). The 5-year actuarial incidence of rectal, bladder, and small bowel late complications was 16%, 11%, and 14%, respectively. Patients treated with cumulative BED at rectum points above 110 Gy 3 and at bladder point above 125 Gy 3 had a higher but not statistically significant 5-year actuarial rate of complications at these organs (18% vs. 12%, p = 0.49 and 17% vs. 9%, p = 0.20, respectively). Patients who received parametrial doses larger than 59 Gy had a higher 5-year actuarial rate of complications in the small bowel; however, this was not statistically significant (19% vs. 10%, p = 0.260). Conclusion: This series suggests that 45 Gy to the whole pelvis combined with four fractions of 6 Gy to point A with HDR brachytherapy is an effective and safe fractionation schedule in the treatment of Stages II and III cervix cancer if realized up to 50 days. To decrease the small bowel complications, we decreased the superior border of the parametrial fields to the S2-S3 level and the total dose to 54 Gy.

A study of relationship between the level of serum squamous cell antigen and recurrence patterns after treatment of uterine cervix cancer

A study of relationship between the level of serum squamous cell antigen and recurrence patterns after treatment of uterine cervix cancer

67 Postoperative radiotherapy with external beam therapy and HDR brachytherapy in the treatment of uterine cervix cancer

67 Postoperative radiotherapy with external beam therapy and HDR brachytherapy in the treatment of uterine cervix cancer

[Development of topical drug delivery systems utilizing polymeric materials].

Topical drug delivery is important from the view points of improvement of therapeutic effect and reduction of systemic side effects. Utilization of polymeric materials seemed to be as a key for the development of new topical dosage forms including targeting drug delivery systems. Adriamycin ointment for local chemotherapy to breast cancer prepared using polyethylene glycol, ammonium polyacrylate and hydroxypropyl cellulose (HPC) according to an optimum formulation showed an excellent clinical effect in spite of a decreased drug content. Double-layered mucoadhesive sticks for the treatment of uterine cervix cancer were prepared by direct compression of powder mixture of bleomycin, HPC and carboxyvinyl polymer (CP). Drug release property of the sticks could be controlled by the weight of outer layer, drug combining ratio to each layer and coating of core layer. The results suggested a possibility of a "once-a-week" treatment that is preferable for the patients. Magnetic granules for the treatment of esophageal cancer were prepared using ferrite, HPC and CP. Magnetic guidance and retainment of the granules on esophageal mucosa were confirmed using rabbits in vivo. Buoyant sustained release preparations were prepared using chitosan, soybean protein, HPC and other polymers. Usefulness of the buoyant preparations was suggested from the results in vitro and in vivo. Insulin microspheres (IMS) for targeting delivery to the small intestine were prepared by the newly developed method. Employment of enteric coating material (Eudragit) and combination of protease inhibitor protected insulin from enzymatic attack and gave decreased levels of blood glucose by oral administration.

Applicator for use of cesium-137 miniaturized tube sources in the treatment of uterine cervix cancer

A modified afterloading Kumar Cervical Applicator with a 3 mm diameter central tandem permits insertion of the afterloading tandem into the uterus without need of manual cervical dilatation. While general anesthesia is required for insertion of standard cervical applicators, this is eliminated because the central tandem is no larger than a uterine sound, and the tandem may be painlessly inserted into the uterus while the patient is awake.

Uterine cervix cancer treatment complications: Preliminary results of a multicentric study

Uterine cervix cancer treatment complications: Preliminary results of a multicentric study

Results of treatment of uterine cervix cancer by radiotherapy

The results of treatment of uterine cervix cancer by radiotherapy alone in 259 patients in the period January 1973 to December 1984 are reported. They are analyzed according to patients age, stage, tumor volume, extent of parametrial infiltration, hydronephrosis and nodal status. It is shown that age, tumor volume, extent of parametrial invasion and nodal metastases are the main prognostic factors. Analysis of pelvic failures shows that external radiotherapy followed by curietherapy seems to be the best method for patients with T 2b and T 3b tumors of small volume (less than 60 mm in diameter), particularly when parametrial infiltration is limited. Patients with T 2b tumors of large volume (barrel shaped) seem to need a more aggressive approach, and a higher number of complications are therefore expected. Patients with T 3b and massive parametrial infiltration, with T 4 and nodal metastases need new and different approaches, possibly including adjuvant chemotherapy.