scholarly journals A retrospective review of conventional versus hypo-fractionated pelvic radiotherapy for locally advanced cervical cancer, in limited-resource countries: The Uganda experience

2021 ◽  
Vol 5 ◽  
Author(s):  
Awusi Kavuma ◽  
Israel Luutu ◽  
Solomon Kibudde ◽  
Cissy Bangidde
Keyword(s):  
Cervical Cancer ◽  
External Beam Radiotherapy ◽  
Locally Advanced ◽  
Limited Resource ◽  
High Volume ◽  
Advanced Cervical Cancer ◽  
Fractionated Radiotherapy ◽  
Locally Advanced Cervical Cancer ◽  
Gynecology And Obstetrics ◽  
Clinical Radiotherapy

Background: Cervical cancer incidence in Uganda is 54.8 per 100 000 population. We annually treat over 800 new cervical cancers (40% of the workload), which is challenging to treat such numbers in limited resources settings. From July 2011, we commenced the use of hypo-fractionated radiotherapy (HFRT) of 45 Gy/15 fraction (#) as an alternative to conventional fractionated radiotherapy (CFRT) of 50 Gy/25#, for treatment of locally advanced cervical cancer (LACC).Aim: To compare the 5-year follow-up treatment outcomes between CFRT and HFRT.Settings: The study analysed patients treated at the Uganda Cancer Institute – a limited resource institution.Methods: This was a non-randomised, retrospective study, where 414 patients’ files were reviewed according to demographic, clinical, radiotherapy fractionations and outcomes. Inclusion criteria were International Federation of Gynecology and Obstetrics stages IIB–IIIB cervical cancer cases and had completed external beam radiotherapy and intracavitary radiotherapy.Results: Squamous cell carcinomas were 93.6% and adenocarcinomas were 3.0%. The median age was 49.5 (interquartile range [IQR]: 40.0–56.0) years. Stages IIB/IIIA/IIIB were 36.2%, 8.2%, 55.6%, respectively. Human immunodeficiency virus serology was positive, negative, and unknown in 70 (16.9%), 116 (28.0%) and 228 (55.1%), respectively. Concurrent chemo-radiation was administered in 182 (44.0%) patients. Conventional fractionated radiotherapy and HFRT were 221 (53.4%) and 193 (46.6%), respectively. At 6 months, the overall response rate was 73.3% for CFRT compared with 67.6% for HFRT (p = 0.085), whilst the grades 0–1 toxicities were 94.5% and for 94.7% CFRT and HFRT, respectively (p = 0.080). At 60 months, the survival probabilities were 44.9% for CFRT and 46.6% for HFRT (p = 0.293).Conclusion: There is no significant statistical difference between CFRT and HFRT for the treatment of LACC. The HFRT could be considered for high volume limited resource settings.

3D HDR intracavitary brachytherapy combined with complementary applicator-guided external beam radiotherapy for 338 patients with stage IIB-IIIB uterine cervical cancer: A single-center phase II prospective study with long-term follow-up.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5530-5530 ◽  
Author(s):  
Jin Yi Lang ◽  
Zixuan Fan ◽  
Peng Xu ◽  
Mei Feng ◽  
Weidong Wang
Keyword(s):  
Cervical Cancer ◽  
External Beam Radiotherapy ◽  
Locally Advanced ◽  
Uterine Cervical Cancer ◽  
Intracavitary Brachytherapy ◽  
External Beam ◽  
Advanced Cervical Cancer ◽  
Locally Advanced Cervical Cancer ◽  
Gynecology And Obstetrics

5530 Background: For uterine cervical cancer (UCC) patients with asymmetric parametric lesions, 3D HDR-intracavitary brachytherapy (HDR-ICBT) could not cover all the lesions, resulting in residual lesion and treatment failure. To settle this problem, a novel treatment modal of 3D HDR-ICBT combined with complementary applicator-guided external beam radiotherapy (EBRT) was used for UCC patients with stage IIB-IIIB in present study. Methods: Between June 2010 and June 2015, 338 patients with locally advanced cervical cancer (International Federation of Gynecology and Obstetrics stage IIB-IIIB) were treated with concurrent chemoradiotherapy. Imaged guided IMRT was used for external beam radiotherapy, 45Gy/25f. The chemotherapy was weekly cisplatin (40mg/m2). Four fractions of 3D HDR-ICBT combined with complementary applicator-guided external beam radiotherapy were used. The prescribed dose for HR-CTV and IR-CTV was 7Gy (D90) and 5Gy (D90). Dose constraints for organs at risk were D2cc <70 Gy for rectum, and D2cc<90 Gy for bladder in terms of equivalent total dose in 2 Gy fractions as GEC-ESTRO recommendations. Results: Median follow-up was 64 months (11–71 months). The D90 of GTV, HR-CTV, and IR-CTV in all cases were 93.4 (85.1-107.8) Gy, 86.4 (79.9-91.3) Gy and 72.3 (70.8-75.2) Gy, respectively. The D2CC of bladder, rectum and sigmoid were 74.3Gy、65.5Gy and 64.1Gy, respectively. 5-year LRC, DFS, and OS was 90.8%, 84.1% and 80.8%, respectively. Treatment was well tolerated. The grade ≥3 genitourinary and gastrointestinal acute and late toxicities were 2.1% and 5.2%, respectively. Conclusions: The combination of HDR-ICBT with an applicator-guided IMRT is feasible for uterine cervical cancer patients with asymmetric parametric lesions. Further study is needed to determine whether this treatment modal could be used to replace the invasive interstitial brachytherapy (ISBT) in the cases of locally advanced cervical cancer where HR-CTV coverage cannot be obtained with ICBT.

Neoadjuvant Chemotherapy With Cisplatin and Gemcitabine Followed by Chemoradiation Versus Chemoradiation for Locally Advanced Cervical Cancer: A Randomized Phase II Trial

2019 ◽  
Vol 37 (33) ◽  
pp. 3124-3131 ◽  
Author(s):  
Samantha Cabral S. da Costa ◽  
Renata Colombo Bonadio ◽  
Flavia Carolina G. Gabrielli ◽  
Andrea S. Aranha ◽  
Maria Luiza N. Dias Genta ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Additional Treatment ◽  
Hazard Ratio ◽  
Advanced Cervical Cancer ◽  
Locally Advanced Cervical Cancer ◽  
Gynecology And Obstetrics

PURPOSE Although chemoradiation therapy (CRT) with cisplatin remains the standard treatment of patients with locally advanced cervical cancer (LACC), 40% of patients present with disease recurrence. Additional treatment strategies are required to improve outcomes. We conducted a trial to evaluate the efficacy and safety of neoadjuvant chemotherapy (NAC) with cisplatin and gemcitabine followed by CRT. METHODS In this phase II trial, patients with LACC (International Federation of Gynecology and Obstetrics stage IIB to IVA or with positive lymph nodes) were randomly assigned to three cycles of NAC with cisplatin and gemcitabine followed by standard CRT with weekly cisplatin plus pelvic radiotherapy or to standard CRT alone. The primary end point was 3-year progression-free survival (PFS). Secondary end points were response rate, 3-year locoregional control, 3-year overall survival (OS), safety, and quality of life. RESULTS From 107 patients enrolled in the trial, 55 were randomly assigned to the NAC arm and 52 to the CRT-alone arm. The majority of patients had squamous cell carcinoma (87.8%). After a median follow-up of 31.7 months, NAC was associated with an inferior PFS, with 3-year PFS rates of 40.9% v 60.4% in the CRT arm (hazard ratio, 1.84; 95% CI, 1.04 to 3.26; P = .033). NAC also was associated with a lower OS (3-year OS rate, 60.7% v 86.8%; hazard ratio, 2.79; 95% CI, 1.29 to 6.01; P = .006). After treatment completion, complete response rates were 56.3% in the NAC arm and 80.3% in the CRT arm ( P = .008). Toxicities were similar in both arms, with the exception of hypomagnesemia and neuropathy being more common with NAC. CONCLUSION This study shows that the addition of NAC consisting of cisplatin and gemcitabine to standard CRT is not superior and is possibly inferior to CRT alone for the treatment of LACC.

Rising Rates of Upfront Surgery in Early Locally Advanced Cervical Cancer: What Factors Predict for This Treatment Paradigm?

2018 ◽  
Vol 28 (8) ◽  
pp. 1560-1568 ◽  
Author(s):  
Arya Amini ◽  
Tyler P. Robin ◽  
Priscilla K. Stumpf ◽  
Chad Rusthoven ◽  
Tracey E. Schefter ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Logistic Regression ◽  
Locally Advanced ◽  
Median Income ◽  
Advanced Cervical Cancer ◽  
Postoperative Radiation Therapy ◽  
Locally Advanced Cervical Cancer ◽  
Gynecology And Obstetrics ◽  
Treatment Paradigm ◽  
Care Costs

ObjectiveIn this study, we analyzed patterns of care for patients with locally advanced cervical cancer to identify predictors for upfront surgery compared with definitive chemoradiation (CRT).MethodsThe National Cancer Database was queried for patients aged 18 years or older with Federation of Gynecology and Obstetrics IB2–IIB cervical cancer. All patients underwent either upfront hysterectomy with or without postoperative radiation therapy versus definitive CRT. Logistic regression was used to assess variables associated with modality of treatment (surgery vs CRT).ResultsOf the 9494 patients included, 2151 (22.7%) underwent upfront surgery. Of those undergoing surgery, 380 (17.7%) had positive margins, 478 (22.2%) had positive nodes, and 458 (21.3%) had pathologic involvement of the parametrium. Under multiple logistic regression, rates of surgery significantly increased from 2004 (12.2%) to 2012 (31.2%) (odds ratio [OR] per year increase, 1.15; confidence interval [CI], 1.12–1.17; P < 0.001). Upfront surgery was more commonly performed in urban (OR, 1.21; 95% CI, 1.03–1.41; P = 0.018) and rural counties (OR, 1.79; 95% CI, 1.24–2.58; P = 0.002), for adenocarcinoma (OR, 2.14; 1.88–2.44; P < 0.001) and adenosquamous (OR, 2.69; 2.11–3.43; P < 0.001) histologies, and in patients from higher median income communities (ORs, 1.19–1.37). Upfront surgery was less common at academic centers (OR, 0.73; 95% CI, 0.58–0.93; P = 0.011).ConclusionsRates of upfront surgery relative to definitive CRT have increased significantly over the past decade. In the setting of level 1 evidence supporting the use of definitive CRT alone for these women, the rising rates of upfront surgery raises concern for both unnecessary surgical procedures with higher rates of treatment-related morbidity and greater health care costs.

ENGOT-cx11/KEYNOTE-A18: A phase III, randomized, double-blind study of pembrolizumab with chemoradiotherapy in patients with high-risk locally advanced cervical cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS6096-TPS6096
Author(s):  
Domenica Lorusso ◽  
Nicoletta Colombo ◽  
Robert L. Coleman ◽  
Leslie M. Randall ◽  
Linda R. Duska ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
High Risk ◽  
External Beam Radiotherapy ◽  
Locally Advanced ◽  
Phase Iii ◽  
Controlled Study ◽  
Double Blind Study ◽  
Advanced Cervical Cancer ◽  
Double Blind ◽  
Locally Advanced Cervical Cancer

TPS6096 Background: High-risk locally advanced cervical cancer has a poor prognosis, and more than half of patients recur in 2 y. External beam radiotherapy (EBRT) with concurrent chemotherapy followed by brachytherapy is the standard of care for locally advanced cervical cancer. The immunostimulatory activity of the PD-1 inhibitor pembrolizumab (pembro) may be enhanced by concurrent chemoradiotherapy (CRT). After the KEYNOTE-158 study, in which pembro showed durable antitumor activity, pembro monotherapy was approved for patients with PD-L1–positive recurrent or metastatic cervical cancer who progressed during or after chemotherapy. ENGOT-cx11/KEYNOTE-A18 (NCT04221945) is a phase III, randomized, placebo-controlled study evaluating pembro with concurrent CRT for the treatment of locally advanced cervical cancer. Methods: Approximately 980 patients with high-risk (FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA), locally advanced, histologically confirmed cervical cancer who have not received systemic therapy, immunotherapy, definitive surgery, or radiation will be randomized 1:1 to receive either 5 cycles of pembro 200 mg every 3 wk (Q3W) + CRT followed by 15 cycles of pembro 400 mg Q6W or 5 cycles of placebo Q3W + CRT followed by 15 cycles of placebo Q6W. The CRT regimen includes 5 cycles (with optional 6th dose) of cisplatin 40 mg/m2 Q1W + EBRT followed by brachytherapy. Randomization is stratified by planned EBRT type (intensity-modulated radiotherapy [IMRT] or volumetric-modulated arc therapy [VMAT] vs non-IMRT or non-VMAT), cancer stage at screening (stage IB2-IIB vs III-IVA), and planned total radiotherapy dose. Treatment will continue until the patient has received 20 cycles of pembro (5 cycles 200 mg Q3W, 15 cycles 400 mg Q6W) vs placebo (~2 y) or until disease progression, unacceptable toxicity, or withdrawal. Primary endpoints are PFS per RECIST v1.1 by blinded independent central review and OS. Secondary endpoints are PFS at 2 y, OS at 3 y, complete response at 12 wk, ORR, PFS and OS in PD-L1–positive patients, EORTC QLQ-C30 and QLQ-CX24, and safety. Enrollment is ongoing. Clinical trial information: NCT04221945.

scholarly journals Computed Tomography–Guided Interstitial Brachytherapy for Locally Advanced Cervical Cancer: Introduction of the Technique and a Comparison of Dosimetry With Conventional Intracavitary Brachytherapy

2017 ◽  
Vol 27 (4) ◽  
pp. 768-775 ◽  
Author(s):  
Zhong-Shan Liu ◽  
Jie Guo ◽  
Yang-Zhi Zhao ◽  
Xia Lin ◽  
Bing-Ya Zhang ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Cervical Cancer ◽  
External Beam Radiotherapy ◽  
Locally Advanced ◽  
High Dose ◽  
External Beam ◽  
Advanced Cervical Cancer ◽  
3 Dimensional ◽  
Locally Advanced Cervical Cancer ◽  
The Mean

ObjectiveWe present a new technique of 3-dimensional computed tomography–guided interstitial (IS) brachytherapy (BT) for locally advanced cervical cancer, offering a more advantageous clinical treatment approach.Materials/MethodsInterstitial BT was performed using an applicator combining uterine tandem and metal needles; needles were inserted freehand under real-time 3-dimensional computed tomography guidance. Twenty-eight patients with bulky tumors and/or parametrial extension (tumor size > 5 cm) after external beam radiotherapy received IS BT. Dosimetric outcomes of the IS BT including the total dose (external beam radiotherapy and high dose-rate BT) D90 for the high-risk clinical target volume (HR-CTV) and D2cc for the organs at risk (OARs) were investigated and compared with a former patient group consisting of 30 individuals who received the conventional intracavitary (IC) BT.ResultsThe mean D90 values for HR-CTV in the IC BT and IS BT groups were 76.9 ± 5.7 and 88.1 ± 3.3 Gy, respectively. Moreover, 85.7% of the patients received D90 for HR-CTV of 87 Gy or greater in the IS BT group, and only 6.7% of the patients received D90 for HR-CTV of 87 Gy or greater in the IC BT group. The D2cc for the bladder, rectum, and sigmoid were 84.7 ± 6.8, 69.2 ± 4.2, and 67.8 ± 4.5 Gy in the IC BT group and 81.8 ± 6.5, 66.8 ± 4.0, and 64.8 ± 4.1 Gy in the IS BT group. The mean number of needles was 6.9 ± 1.4, with a mean depth of 2.9 ± 0.9 mm for each IS BT. Interstitial BT was associated with only minor complications.ConclusionsThe IS BT technique resulted in better dose-volume histogram parameters for large volume tumors (>5 cm) compared with the conventional IC BT and acceptable risk of acute complications in locally advanced cervical cancer and is clinically feasible.

Individually customised parametrial boost for locally advanced cervical cancer: is 2D planned external beam radiotherapy useful?

2019 ◽  
Vol 19 (3) ◽  
pp. 248-253
Author(s):  
Aparna Gangopadhyay ◽  
Subrata Saha
Keyword(s):  
Cervical Cancer ◽  
External Beam Radiotherapy ◽  
Locally Advanced ◽  
Intracavitary Brachytherapy ◽  
External Beam ◽  
Advanced Cervical Cancer ◽  
Locally Advanced Cervical Cancer ◽  
Pelvic Wall ◽  
Significant Difference ◽  
Median Period

AbstractAim:Pelvic wall control and toxicity was retrospectively assessed in patients who received individually customised parametrial boost (PMB) for locally advanced cervical cancer with 2D planned external beam radiotherapy. Outcomes of a dose-escalated combined boost were also evaluated.Materials and methods:Toxicity and pelvic wall recurrence was evaluated over a median period of 24 months between two groups who received different pelvic wall doses. One group was randomised to receive either intracavitary brachytherapy (ICRT) with an external beam PMB using a customised midline shield, or a dose-escalated combined boost with interstitial brachytherapy (ISBT) and PMB. The comparator group received no PMB.Results:At 24 months, pelvic wall recurrence occurred in 2/112 and 40/130 with and without PMB, respectively (p < 0·000001). No significant difference in toxicity was noted between boost versus no-boost groups (p = 0·56). Combined ISBT/PMB dose escalation showed no significant difference in pelvic wall recurrence compared with PMB alone (p = 0·49).Findings:Individually customised 2D PMBs with 3D image-based ICRT was safe and improved pelvic wall control in locally advanced cervix cancer. Dose-escalated combined boosts offered no significant benefit over standard boost doses.

Laparoscopic Extrafascial Hysterectomy (Completion Surgery) After Primary Chemoradiation in Patients With Locally Advanced Cervical Cancer: Technical Aspects and Operative Outcomes

2014 ◽  
Vol 24 (3) ◽  
pp. 608-614 ◽  
Author(s):  
Giovanni Favero ◽  
Juliana Pierobon ◽  
Maria Luiza Genta ◽  
Marcia Pereira Araújo ◽  
Giovanni Miglino ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Residual Disease ◽  
Locally Advanced ◽  
International Federation ◽  
Advanced Cervical Cancer ◽  
Histologic Finding ◽  
Locally Advanced Cervical Cancer ◽  
Gynecology And Obstetrics ◽  
Completion Surgery ◽  
The Mean

ObjectiveThis study aimed to evaluate the feasibility and safety of laparoscopic extrafascial hysterectomy and bilateral salpingo-oophorectomy after primary chemoradiation (CRT) in patients with locally advanced cervical cancer (LACC) without evidence of nodal metastasis.BackgroundCurrently, the standard of care for patients with advanced cervical cancer is concurrent CRT. There is an unequivocal correlation between presence of residual disease and risk of local relapse. Nevertheless, the importance of hysterectomy in adjuvant setting remains controversial.MethodsProspective study with patients affected by bulky LACC (International Federation of Gynecology and Obstetrics stage IB2 up to IIB) treated initially with radical CRT who underwent laparoscopic surgery 12 weeks after therapy conclusion. Inclusion criteria were absence of signs for extrapelvic or nodal involvement on initial imaging staging, as well as complete clinical and radiologic response.ResultsFrom January 2011 to March 2013, 33 patients were endoscopically operated. The mean age was 44 years (range, 21–77 years). Histologic finding revealed squamous cell carcinoma in 19 (60%) cases and adenocarcinoma in 14 (40%) cases. International Federation of Gynecology and Obstetrics stages distribution were as follow: 1B2, n = 3 (9%); IIA, n = 4 (11%); and IIB, n = 26 (80%). The mean pretherapeutic tumor size was 5.2 cm (range, 4–10.2 cm). Estimated blood loss was 80 mL (range, 40–150 mL), and mean operative time was approximately 104 minutes (range, 75–130 minutes). No casualty or conversion to laparotomy occurred. Hospital stay was in average 1.7 days (range, 1–4 days). Significant complication occurred in 12% of the cases; 2 vaginal vault dehiscence, 1 pelvic infection, and 1 ureterovaginal fistula. Nine (27%) patients had pathologic residual disease, and in 78% of these cases, histologic finding was adenocarcinoma (P = −0.048). All patients had free margins. After median follow-up of 16 months, all women have no signs of local recurrence.ConclusionsLaparoscopic extrafascial hysterectomy (completion surgery) after primary CRT in patients with apparent node-negative LACC is a feasible and safe strategy to improve tumor local control mainly in cases of adenocarcinoma.

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