Prophylactic Para-aortic Irradiation Research Articles

Do Radiotherapy Planning Factors Influence Para-Aortic Recurrence in IIIC1 Cervical Cancer Patients?

Patients with locally advanced cervical cancer are at higher risk of para-aortic lymph node recurrence, however, the addition of prophylactic para-aortic irradiation is still controversial. The aim of this study was to evaluate prognostic factors related to para-aortic recurrence in patients with cervical cancer and pelvic lymph node metastasis (2018 FIGO Stage IIIC1).A retrospective cohort analysis was conducted with patients with cervical cancer and pelvic lymph node metastasis (2018 FIGO Stage IIIC1), that were treated with primary or adjuvant chemoradiotherapy from 2007 to 2018 at a single tertiary cancer center. Clinical and pathological variables were evaluated, as well as radiological and radiotherapy planning factors. Kaplan-Meier method was used to calculate survival and survival comparison between groups with log-rank method. Statistically significant was defined as P ≤ 0.05.Seventy-two patients were included: 56 (77.8%) had primary chemoradiotherapy and 16 (22.2%) adjuvant chemoradiotherapy after radical hysterectomy and lymph node staging. 58 (80.5%) underwent 3D-conformal, 14 (19.5%) intensity-modulated radiotherapy, and 67 (93%) also had high dose rate vaginal brachytherapy. Only 1 patient did not receive concomitant chemotherapy. Staging PET-CT was available in 23 (31.9%) cases and the remaining ones were staged with MRI or CT scans, Surgical para-aortic staging was not performed. The median follow-up was 42 months (range, 5 to 144 months). Overall, 27 (37.5 %) patients recurred during follow-up, and 7 (26 %) had isolated para-aortic lymph-node recurrence. Distant metastasis and pelvic recurrence were found in 12 (45 %) and 8 (29 %) cases, respectively. Median overall survival, disease free survival, distant metastasis free survival, loco-regional free survival and para-aortic free survival were 56, 52, 52, 51 and 42 months, respectively. In univariate analysis, PET SUV in pelvic lymph nodes higher than 10.2 (P = 0.02) and positive lymph nodes in the left common iliac station (P = 0.05) were identified as predictive factors for isolated para-aortic recurrence. We also identified positive lymph node in the common iliac station as a predictor for distant recurrence (P = 0.002). Tumor size larger than 66 mm (P = 0.046) and positive lymph node in the left common iliac lymph node station (P = 0.02) as predictors for pelvic recurrence. Lymph node > 24 mm was the only prognostic factor associated with overall survival (P = 0.012).In this retrospective cohort, radiological and radiotherapy planning factors as high lymph node's PET SUV and proximal location of positive pelvic lymph nodes were prognostic for para-aortic recurrence in IIIC1 cervical cancer patients. Further prospective and randomized studies are required to validate those risk factors as well as to determine if prophylactic para-aortic irradiation would improve outcomes in these patients.P.J. Pinto: None. S.L. Favareto: None. C.F. Souza: None. G. Baiocchi: None. A.A. da Costa: None. A.C. Pellizon: None. C. Abrahao: None. D.G. Castro: None. G.R. Gondim: None. H. Ramos: None. E. Santos Neto: None. R.C. Fogaroli: None. M.G. Silva: None. M.J. Chen: None.

Diagnosis and treatment of para-aortic lymph node metastasis in cervical cancer

Para-aortic lymph node metastasis is one of the main prognostic factors for cervical cancer. The para-aortic lymph node metastatic rate increases with the progression of disease stage. Therefore, an important approach for improving the prognosis in cervical cancer patients with para-aortic lymph node metastasis is early diagnosis followed by proper therapy, as well as prophylactic para-aortic irradiation in high-risk patients. Key words: Cervical neoplasms; Lymph node metastasis; Diagnostics; Therapeutics

Radiation therapy oncology group gynecologic oncology working group: comprehensive results.

The purpose of this report was to comprehensively describe the activities of the Gynecologic Oncology Working Group within the Radiation Therapy Oncology Group (RTOG). Clinical trials will be reviewed as well as translational science and ancillary activities. During the past 40 years, a myriad of clinical trials have been performed within the RTOG with the aim of improving overall survival (OS) and decreasing morbidity in women with cervical or endometrial cancer. Major study questions have included hyperbaric oxygen, neutron radiotherapy, altered fractionation, hypoxic cell sensitization, chemosensitization, and volume-directed radiotherapy.RTOG 7920 demonstrated improvement in OS in patients with stages IB through IIB cervical carcinoma receiving prophylactic para-aortic irradiation compared to pelvic radiation alone. RTOG 9001 demonstrated that cisplatin and 5-FU chemoradiotherapy to the pelvis for advanced cervix cancer markedly improved OS compared to extended field radiotherapy alone. More recent trials have used radioprotectors, molecular-targeted therapy, and intensity-modulated radiation therapy. Ancillary studies have developed clinical target volume atlases for research protocols and routine clinical use. Worldwide practice patterns have been investigated in cervix, endometrial, and vulvar cancer through the Gynecologic Cancer Intergroup. Translational studies have focused on immunohistochemical markers, changes in gene expression, and miRNA patterns impacting prognosis.The RTOG gynecologic working group has performed clinical trials that have defined the standard of care, improved survival, and added to our understanding of the biology of cervical and endometrial cancers.

Effects of Concurrent Chemotherapy and Postoperative Prophylactic Paraaortic Irradiation for Cervical Cancer with Common Iliac Node Involvement

Effects of Concurrent Chemotherapy and Postoperative Prophylactic Paraaortic Irradiation for Cervical Cancer with Common Iliac Node Involvement

Effects of Postoperative Prophylactic Paraaortic Irradiation in Cervical Cancer with Common Iliac Nodal Involvement

Effects of Postoperative Prophylactic Paraaortic Irradiation in Cervical Cancer with Common Iliac Nodal Involvement

Prospective Phase II Trial of Prophylactic Para-Aortic Irradiation and Concurrent Chemotherapy in Cervical Cancer

Prospective Phase II Trial of Prophylactic Para-Aortic Irradiation and Concurrent Chemotherapy in Cervical Cancer

Irradiation of Pelvic and Para-Aortic Nodes in Carcinoma of the Cervix.

Extended-field irradiation offers a significant chance of cure for patients with para-aortic node metastases if pelvic disease can be controlled. Prognosis is best for patients with microscopic para-aortic disease or with a single enlarged node. Complications of extended-field irradiation can be minimized with careful radiation therapy technique that uses multiple fields and high-energy beams of 18 MV or greater and by avoiding transperitoneal surgical staging. Although the role of prophylactic para-aortic irradiation is still being defined, randomized trials suggest that extended fields do benefit some patients with locoregionally advanced disease.

Feasibility of concurrent cisplatin and extended field radiation therapy (EFRT) using intensity modulated radiotherapy for carcinoma of the cervix

The orderly nodal pattern of spread of cervical cancer has generated interest in prophylactic paraaortic irradiation. A single cooperative group study demonstrated a potential clinical benefit with this approach at the cost of increased acute and late toxicity. Recent data confirming an advantage for chemoradiation has further complicated the picture. The RTOG experience with extended field radiation therapy (EFRT) with concurrent chemotherapy for carcinoma of the cervix has been associated with unacceptably high acute morbidity.

Feasibility of concurrent cisplatin and extended field radiation therapy (EFRT) using intensity modulated radiotherapy for carcinoma of the cervix

The orderly nodal pattern of spread of cervical cancer has generated interest in prophylactic paraaortic irradiation. A single cooperative group study demonstrated a potential clinical benefit with this approach at the cost of increased acute and late toxicity. Recent data confirming an advantage for chemoradiation has further complicated the picture. The RTOG experience with extended field radiation therapy (EFRT) with concurrent chemotherapy for carcinoma of the cervix has been associated with unacceptably high acute morbidity.

Long-term clinical outcomes of postoperative pelvic radiotherapy with or without prophylactic paraaortic irradiation for stage I-II cervical carcinoma with positive lymph nodes: retrospective analysis of predictive variables regarding survival and failure patterns.

We performed retrospective analysis to classify the risk hazard of patients with stage I-II cervical cancer with lymph node metastases treated with postoperative radiotherapy. From 1981 to 1995, 106 patients with early stage cervical carcinoma who received adjuvant pelvic radiation were entered in the analysis. The median patient age was 53.0 years (range 21-73). The median dose of 45.3 Gy (range, 32.1-56.4 Gy) was delivered over the whole pelvis. Seventy patients also received prophylactic paraaortic radiation (median 44 Gy; range 22-46 Gy). The 5/10-year overall survival (OAS), disease-free survival (DFS), pelvic control, and distant metastasis-free survival rates were 69.1/63.5%, 62.4/58.1%, 85.7/84.3%, and 74.1/71.6%, respectively. In the uni-/multivariate analyses, the significant prognostic factors of OAS and DFS proved to be disease stage, duration period between operation and radiotherapy, histology, and presence or absence of common iliac lymph node metastasis. Using the results of these analyses, we devised a predictive model for DFS. In this model, the 5-year DFS rates of patients with low (N = 35), intermediate (N = 59), and high-risk factors (N = 12) were 88.1%, 56.7%, and 16.7%, respectively (p < 0.0001). The majority of analyzed patients did not have adequate DFS estimates in this series. High-risk patients should receive a more intensive strategy, such as concurrent chemoradiotherapy. On the other hand, the effort to reduce toxicity should be considered carefully.

Radiation Therapy Oncology Group clinical trials for carcinoma of the cervix.

Grigsby PW. Radiation Therapy Oncology Group clinical trials for carcinoma of the cervix. The purpose of this paper is to review the primary data of the clinical trials performed by the Radiation Therapy Oncology Group (RTOG) for patients with carcinoma of the uterine cervix. The trials, their strengths, limitations, and the implications of the results are discussed. During the past 25 years there have been several clinical trials performed by the RTOG to test various hypotheses for improving local control and survival for patients with carcinoma of the uterine cervix. The major research themes that have been appraised are the use of hyperbaric oxygen, altered fractionation radiotherapy, hypoxic cell sensitization, chemo-sensitization, prophylactic paraaortic irradiation, and neutron radiotherapy. There are two general research themes. The initial RTOG trials for cervical cancer attempted to address the issues of tumor volume and hypoxic cells while the latter studies addressed these issues and the issue of micrometastatic disease. The phase III clinical trials performed by the RTOG have not demonstrated a local control or survival advantage in the experimental arm with the use of hyperbaric oxygen, split-course radiotherapy, hypoxic cell sensitization, or neutron radiotherapy. Acceptable toxicity and efficacy results were shown in phase II studies evaluating twice-daily irradiation and chemo-sensitization. The positive phase III trials were RTOG 79-20 which evaluated prophylactic paraaortic irradiation in patients with bulky stages IB, IIA, and IIB disease, and RTOG 90-01 which evaluated concurrent chemotherapy. Results of more recent clinical trials are pending their completion.

Mantle irradiation alone for selected patients with laparotomy-staged IA to IIA Hodgkin's disease: preliminary results of a prospective trial.

To determine the feasibility of omitting prophylactic paraaortic irradiation in selected patients with laparotomy-staged (pathologically staged [PS]) IA to IIA Hodgkin's disease. We initiated a prospective single-arm trial in October 1988 to study the role of mantle irradiation alone in selected PS IA to IIA patients with Hodgkin's disease. A total of 37 patients have been entered onto this trial. Entrance criteria included nodular sclerosis (NS) or lymphocyte predominance (LP) histology, absence of B symptoms, disease limited above the carina, and a negative laparotomy. Results of treatment of 23 patients in the prospective trial, monitored off treatment for > or = 1 year, are presented. Twenty-three additional PS IA to IIA patients, treated with mantle irradiation alone from 1970 to 1987, were analyzed as a comparison group. The median follow-up durations were 32 and 113 months, respectively, for the two groups. The 4-year actuarial rates of freedom from relapse and overall survival are 83% and 100%, respectively, for the prospective trial. The 10-year actuarial rates of freedom from relapse and overall survival are 83% and 89%, respectively, for retrospectively studied patients. There have been five recurrences among 46 patients who received mantle irradiation alone, all with a component of relapse below the diaphragm. These early results support the use of mantle irradiation alone in selected PS IA to IIA patients with NS or LP histology. Relapses, although rare, have occurred predominantly below the diaphragm. This suggests the need for continued long-term surveillance of abdominal and pelvic nodes in this group of treated patients.

Node-positive cervical cancer: Impact of pelvic irradiation and patterns of failure

Purpose : The roles of postoperative pelvic and prophylactic paraaortic irradiation in pelvic node positive cervical cancer are currently controversial. A retrospective study was undertaken to examine the effect of pelvic irradiation on pelvic control and survival and to analyze the patterns of recurrence to determine whether indications exist for prophylactic paraaortic irradiation. Methods and Materials : From 1964 to 1991, 143 cases of FIGO Stage I and II cervical cancer undergoing explanatory laparotomy, pelvic lymph node dissection, and radical hysterectomy had positive pelvic lymph nodes. Postoperatively, 108 cases were treated with whole pelvic irradiation while 35 patients were observed. Prophylactic paraaortic irradiation was not given. Results : Patients who received postoperative whole pelvic irradiation compared with those treated with radical hysterectomy alone had a significantly improved pelvic control rate, disease-free survival (DFS), and overall survival. The 5-year actuarial pelvic control rate was 78% vs. 45% ( p = <0.0001), respectively. The 5-year actuarial DFS was 65% vs. 41% ( p = 0.0004). The 5-year actuarial overall survival was 58% vs 46% ( p = 0.02). In multivariate analysis, pelvic irradiation continued to show a positive effect on DFS ( p = 0.0001) and overall survival ( p = 0.0035). Lymphatic invasion and the total number of positive lymph nodes were the only other independent predictors of overall survival and DFS. The actuarial 5-year pelvic, paraaortic, and distant failure rates were 30%, 10%, and 28%, respectively. An isolated first recurrence in the paraaortic nodes occurred in only three cases. Conclusion : Postoperative pelvic irradiation significantly improves pelvic control, DFS, and overall survival, and should be used in patients with early stage cervical cancer and pathologically proven pelvic nodal metastases. The low incidence of isolated paraaortic nodal failure calls into question the value of routine porphylactic paraaortic irradiation in these patients.

Irradiation of pelvic and para-aortic nodes in carcinoma of the cervix

Extended-field irradiation offers a significant chance of cure for patients with para-aortic node metastases if pelvic disease can be controlled. Prognosis is best for patients with microscopic para-aortic disease or with a single enlarged node. Complications of extended-field irradiation can be minimized with careful radiation therapy technique that uses multiple fields and highenergy beams of 18 MV or greater and by avoiding transperitoneal surgical staging. Although the role of prophylactic para-aortic irradiation is still being defined, randomized trials suggest that extended fields do benefit some patients with locoregionally advanced disease.

Is prophylactic para-aortic irradiation worthwhile in the treatment of advanced cervical carcinoma? Results of a controlled clinical trial of the EORTC radiotherapy group

From November 1977 to July 1981, 441 patients with cervical carcinoma were randomized between pelvic irradiation and pelvic and para-aortic irradiation. Included were patients with stage I and IIB with proximal vaginal and/or parametrial involvement with positive pelvic lymph nodes either on lymphangiogram or at surgery, and stage IIB with distal vaginal and/or parametrial involvement and III regardless of pelvic node status on lymphangiogram. Patients with clinically or surgically involved para-aortic nodes were not included. The external beam dose to the para-aortic area was fixed at 45 Gy. There was no tatistically significant difference between the two treatment arms in terms of local control, overall distant metastases and survival with no evidence of disease (NED), although the incidence of para-aortic metastases and distant metastases without tumor at pelvic sites was significantly higher in patients receiving pelvic irradiation alone (pelvic group). The 4-year NED survival rate was 51%. The incidence of severe digestive complications was significantly higher in patients receiving para-aortic irradiation (para-aortic group). Routine para-aortic irradiation for all high risk patients with cervical carcinoma is of limited value, but patients with a high probability of local control can benefit from extended field irradiation, despite an increase in severe digestive complications.

Is Prophylactic Para-Aortic Irradiation Worthwhile in the Treatment of Advanced Cervical Carcinoma? Results of a Controlled Clinical Trial of the EORTC Radiotherapy Group: Radiotherapy and Oncology, Journal of the European Society for Therapeutic Radiology and Oncology, Vol. 11, 1988, pp. 101–112

Is Prophylactic Para-Aortic Irradiation Worthwhile in the Treatment of Advanced Cervical Carcinoma? Results of a Controlled Clinical Trial of the EORTC Radiotherapy Group: Radiotherapy and Oncology, Journal of the European Society for Therapeutic Radiology and Oncology, Vol. 11, 1988, pp. 101–112

Hodgkin's disease in children. Results of therapy in a mixed group of 178 clinical and pathologically staged patients over 13 years.

One hundred seventy-eight previously untreated children with biopsy-proven Hodgkin's disease of clinical Stages I and II were treated and followed between 1965 and 1978. Staging laparotomy was performed in 30 patients. Ninety-four percent of the patients obtained a complete remission; 24 patients have died. The actuarial survival rate for all patients was 90% at 5 years, and 81% at 10 years. The disease-free survival rate was 69% at 5 years, and 65% at 10 years. When nitrogen mustard, vincristine, procarbazine, and prednisone (MOPP) chemotherapy was added to either extended field or involved field irradiation, the relapse rate was significantly decreased as compared with the protocols without MOPP and prophylactic para-aortic irradiation. The authors believe that surgical staging may not be necessary as splenic involvement may be treated in some patients by MOPP chemotherapy alone or in association with splenic paraaortic radiotherapy. However, the side effects of MOPP need further study by other chemotherapy programs.

Hodgkin's disease in children. Results of therapy in a mixed group of 178 clinical and pathologically staged patients over 13 years

One hundred seventy-eight previously untreated children with biopsy-proven Hodgkin's disease of clinical Stages I and II were treated and followed between 1965 and 1978. Staging laparotomy was performed in 30 patients. Ninety-four percent of the patients obtained a complete remission; 24 patients have died. The actuarial survival rate for all patients was 90% at 5 years, and 81% at 10 years. The disease-free survival rate was 69% at 5 years, and 65% at 10 years. When nitrogen mustard, vincristine, procarbazine, and prednisone (MOPP) chemotherapy was added to either extended field or involved field irradiation, the relapse rate was significantly decreased as compared with the protocols without MOPP and prophylactic para-aortic irradiation. The authors believe that surgical staging may not be necessary as splenic involvement may be treated in some patients by MOPP chemotherapy alone or in association with splenic paraaortic radiotherapy. However, the side effects of MOPP need further study by other chemotherapy programs.