Positive Pelvic Nodes Research Articles

Dose-escalated pelvic radiotherapy for prostate cancer in definitive or postoperative setting.

Given the absence of standardized planning approach for clinically node-positive (cN1) prostate cancer (PCa), we collected data about the use of prophylactic pelvic irradiation and nodal boost. The aim of the present series is to retrospectively assess clinical outcomes after this approach to compare different multimodal treatment strategies in this scenario. Data from clinical records of patients affected by cN1 PCa and treated in six different Italian institutes with prophylactic pelvic irradiation and boost on pathologic pelvic lymph nodes detected with CT, MRI or choline PET/CT were retrospectively reviewed and collected. Clinical outcomes in terms of overall survival (OS) and biochemical relapse-free survival (b-RFS) were explored. The correlation between outcomes and baseline features (International Society of Urological Pathology-ISUP pattern, total dose to positive pelvic nodes ≤ / > 60Gy, sequential or simultaneous integrated boost (SIB) administration and definitive vs postoperative treatment) was explored. ISUP pattern < 2 was a significant predictor of improved b-RFS (HR = 0.3, 95% CI 0.1220-0.7647, P = 0.0113), while total dose < 60Gy to positive pelvic nodes was associated with worse b-RFS (HR = 3.59, 95% CI 1.3245-9.741, P = 0.01). Conversely, treatment setting (postoperative vs definitive) and treatment delivery technique (SIB vs sequential boost) were not associated with significant differences in terms of b-RFS (HR = 0.85, 95% CI 0.338-2.169, P = 0.743, and HR = 2.39, 95% CI 0.93-6.111, P = 0.067, respectively). Results from the current analysis are in keeping with data from literature showing that pelvic irradiation and boost on positive nodes are effective approaches. Upfront surgical approach was not associated with better clinical outcomes.

Disease Characteristics and Patterns of Failure by Histologic Type for Patients Treated With Definitive Radiation for Cervical Cancer

To assess differences in disease characteristics at the time of diagnosis and patterns of failure by histologic subtype following definitive therapy for cervical cancer.Patients with cervical cancer who received definitive radiation between 2004 and 2017 at a single institution were identified. Concurrent chemotherapy was given at the discretion of the treating gynecologic oncologist with consideration of performance status and medical comorbidities. Details regarding disease characteristics, treatment parameters, and patient outcomes were collected. Patients were staged according to the 2009 FIGO staging criteria; and, details regarding the presence of clinically positive pelvic or para-aortic lymph nodes were included (currently, considered FIGO IIICI and IIIC2). Patients were divided between squamous (SCC) and non-squamous histologies (non-SCC) for outcome and disease characteristic analysis. Kaplan-Meier (KM) method was used to estimate progression free survival (PFS), distant metastasis free survival (DMFS), and overall survival (OS). A Cox proportional hazards model was utilized to identify if histologic type was associated with patient outcomes.266 patients who received definitive radiation were identified with a median follow up of 34 months. 94% of patients received cisplatin based concurrent chemotherapy. 216 (81%) had squamous cell carcinoma, 36 (14%) had adenocarcinoma, 13 (5%) had adenosquamous carcinoma, and one patient had had a neuroendocrine small cell tumor. Patients with SCC were more likely than those with non-SCC to have involved lymph nodes (50% vs 36%, P = 0.047) and have FIGO Stage II-IVA disease (57% vs 42%, P = 0.016). The KM estimated 5-year PFS (57% vs 64%), DMFS (61% vs 71%), and OS (65% vs 71%) were not significantly different between those with SCC and non-SCC. On multivariable analysis, histologic distinction of SCC or non-SCC was not associated with PFS, DMFS, or OS. Increasing FIGO stage was associated with worse PFS (HR 1.2 per stage increase, 95% CI 1.1-1.3, P = 0.001), DMFS (HR 1.2 per stage increase, 95% CI 1.1-1.3, P = 0.001), and OS (HR 1.2 per stage increase, 95% CI 1.1-1.4, P < 0.0001). The presence of clinically positive para-aortic lymph nodes was also associated with worse PFS (HR 4.3 compared to no nodes, 95% CI 2.5-7.4, P < 0.0001), DMFS (HR 4.8 compared to no nodes, 95% CI 2.7-8.6, P < 0.0001), OS (HR 4.0 compared to no nodes, 95% CI 2.1-7.4, P < 0.0001) CONCLUSION: In a large single institution database, patients with non-SCC cervical cancer were more likely to present with earlier stage disease (FIGO Stage I) and were less likely to have clinically positive lymph nodes. However, despite the earlier presentation of these non-SCC patients, there was no difference in PFS, DMFS, or OS between the groups. Consideration of additional treatments, including variations in systemic therapy, dose escalation, or surgery, should be evaluated for non-SCC histology cervical cancer patients to improve outcomes in the future.D.F. Cousins: None. J. Sanders: None. D.A. Muller: None. K.A. Ward: None. E. Asare: None. B. Libby: None. T.N. Showalter: Research Grant; Varian Medical Systems. board member and committee chair in ABS; American Brachytherapy Society. K. Romano: None.

Intensity Modulated Radiation Therapy and Concurrent Chemotherapy for Locally Advanced Cervical Cancer Not Amenable to Brachytherapy

<h3>Hypothesis</h3> Cervical cancer patients ineligible for brachytherapy due to tumor geometry suffer poor local control and survival outcomes despite treatment with concurrent IMRT and chemotherapy. <h3>Purpose/Objective(s)</h3> In this study of patients with cervical cancer tumors too large for brachytherapy boost, we report tumor control and toxicity outcomes of patients treated with intensity modulated radiation therapy (IMRT) and concurrent chemotherapy. <h3>Materials/Methods</h3> We performed a retrospective study of patients with FIGO 2018 stage III-IVB cervical cancer treated with high dose IMRT and concurrent cisplatin without brachytherapy at a tertiary academic center from 2005 – 2020. All patients underwent FDG-PET/CT and were examined by an experienced gynecologic brachytherapist. Patients received 48.6-50.4 Gy in 25 to 35 fractions to the cervix, pelvis, and if involved on FDG-PET, paraaortic, and supraclavicular lymph nodes with IMRT. Lymph nodes greater than 3 cm received a simultaneous boost to a total dose of 60 Gy. The primary metabolically active cervical tumor received a simultaneous or sequential boost without additional planning margin to a total dose of 60-70.2 Gy with concurrent weekly cisplatin or carboplatin. Toxicity is reported with CTCAEv5. <h3>Results</h3> Twenty patients out of 1005 (2%) were identified with median age of 55 (range 37 – 76) years. Sixty percent were Caucasian, 35% black, 5% Asian. Median metabolic primary tumor volume was 111 cm3 (range 26 – 473). Nineteen (95%) had squamous histology and one (5%) had adenosquamous. Median follow up was 15 months (range 2 - 154). 7 (35%) patients had PET positive pelvic lymph nodes, 5 (25%) paraaortic, and 3 (15%) supraclavicular. Classic FIGO stage was: III 7 (35%), IVA 11 (55%), IVB 2 (10%). FIGO 2018 stage was: III 3 (15%), IVA 9 (45%), IVB 8 (40%). Five (20%) patients were disease free at the end of follow up (III 1 (33%), IVA 3 (33%), IVB 1 (13%)). One- and 2-year freedom from local progression were 70% and 60%, respectively. One and 2-year OS were 60% and 35%, respectively. Grade 3 anemia and nausea occurred in 4 (20%), and 2 (10%) patients, respectively. Grade 4 diarrhea and nausea occurred in 1 (5%) and 3 (15%) patients, respectively. Two (10%) patients died of treatment-related toxicity. <h3>Conclusion</h3> Our study shows that patients ineligible for brachytherapy suffer poor local control and survival outcomes. Grade 4-5 toxicity occurred in 25% of patients. Novel radiation techniques for this patient population should be further explored.

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.

The annual recurrence risk model for tailored surveillance strategy in patients with cervical cancer

PurposeCurrent guidelines for surveillance strategy in cervical cancer are rigid, recommending the same strategy for all survivors. The aim of this study was to develop a robust model allowing for individualised surveillance based on a patient's risk profile. MethodsData of 4343 early-stage patients with cervical cancer treated between 2007 and 2016 were obtained from the international SCCAN (Surveillance in Cervical Cancer) consortium. The Cox proportional hazards model predicting disease-free survival (DFS) was developed and internally validated. The risk score, derived from regression coefficients of the model, stratified the cohort into significantly distinctive risk groups. On its basis, the annual recurrence risk model (ARRM) was calculated. ResultsFive variables were included in the prognostic model: maximal pathologic tumour diameter; tumour histotype; grade; number of positive pelvic lymph nodes; and lymphovascular space invasion. Five risk groups significantly differing in prognosis were identified with a five-year DFS of 97.5%, 94.7%, 85.2% and 63.3% in increasing risk groups, whereas a two-year DFS in the highest risk group equalled 15.4%. Based on the ARRM, the annual recurrence risk in the lowest risk group was below 1% since the beginning of follow-up and declined below 1% at years three, four and >5 in the medium-risk groups. In the whole cohort, 26% of recurrences appeared at the first year of the follow-up, 48% by year two and 78% by year five. ConclusionThe ARRM represents a potent tool for tailoring the surveillance strategy in early-stage patients with cervical cancer based on the patient's risk status and respective annual recurrence risk. It can easily be used in routine clinical settings internationally.

Comparison of Outcomes and Prognostic Factors Between Early-Stage Cervical Adenocarcinoma and Adenosquamous Carcinoma Patients After Radical Surgery and Postoperative Adjuvant Radiotherapy.

PurposeNo consensus has been reached regarding the survival difference between cervical adenocarcinoma (ADC) and adenosquamous carcinoma (ASC) patients. The purpose of this study was to compare survival outcomes and prognostic factors between early-stage ADC and ASC patients.Patients and MethodsWe retrospectively reviewed stage IB-IIA patients with ADC and ASC who underwent radical hysterectomy and postoperative radiotherapy between June 2012 and December 2017.ResultsA total of 125 patients were enrolled in our study (97 with ADC and 28 with ASC). The median follow-up period was 53.4 months. Compared with ASC patients, patients with ADC tended to have a higher proportion of positive pelvic lymph nodes (7.1% and 26.8%, respectively; p = 0.028). The most common site of distant metastasis was the lung, followed by the intestine and colon. The 5-year overall survival (OS), disease-free survival (DFS), pelvic control, and distant control rates for ADC and ASC patients were 83.6% and 92.0% (p = 0.349), 77.5% and 87.7% (p = 0.279), 81.8% and 96.2% (p = 0.121), and 88.3% and 87.7% (p = 0.948), respectively. Parametrial invasion was a prognostic factor for OS. Lymphovascular space involvement was a prognostic factor for DFS.ConclusionADC patients were more likely to have positive pelvic lymph nodes than those with ASC. There was no significant difference in survival outcomes between patients with ADC and ASC.

Prophylactic ligation of uterine arteries at its origin in laparoscopic surgical staging for endometrial cancer.

The aim of this study was to compare the surgical outcomes between patients who were staged laparoscopically for early-stage endometrioid-type endometrial cancer (EC) between those who underwent prophylactic ligation of uterine arteries (UAs) prior to pelvic lymphadenectomy and the patients who were operated with standard procedure. This retrospective study was conducted in women diagnosed with early-stage and low/intermediate-risk endometrioid-type EC. The control group included patients who underwent standard laparoscopic pelvic lymphadenectomy and the study group concerned patients who underwent prophylactic ligation of UA prior to pelvic lymphadenectomy. The prophylactic ligation of UA procedure was performed at a point just proximal to its origin. The mean lymph node count dissected in the study group was higher in terms of statistical significance (17.5 ± 2.2 vs. 19.8 ± 3.6, p=0.003 and p˂0.05). The rate of the patients who had a positive pelvic lymph node detected did not differ between groups (7.4% vs. 16.7%, p=0.258 and p˂0.05). The operation time (OT) of the patients in the study group did not differ between groups (p=0.546 and p˂0.05). Hemoglobin drop (-0.5 ± 0.7) and hematocrite drop (-0.8 ± 0.9) values in the study group were found to be lower in the study group (p=0.000, p=0.000, and p˂0.05). Performing prophylactic ligation of UA at its origin prevents unwanted bleeding and facilitates the laparoscopic pelvic lymphadenectomy procedure.

Impact of lymphadenectomy and intraoperative tumor rupture on survival in early-stage mucinous ovarian cancers

<h3>Objectives:</h3> Mucinous ovarian carcinoma (MOC) is a rare subtype of epithelial ovarian cancer and often presents a management conundrum. The aim of the study was to investigate the prognostic significance of lymphadenectomy and intraoperative rupture on patient survival. <h3>Methods:</h3> We conducted a retrospective cohort study of all MOCs diagnosed between 1999 and 2019 at two tertiary care cancer centers. Pathology was reviewed to rule out cases with metastasis from gastrointestinal tract primary. Baseline demographics, surgical management details, and outcomes were collected. Five-year overall survival (OS) and recurrence free survival (RFS) were calculated from Kaplan-Meier curves and comparisons made using log-rank test. Cox proportional hazard models were used to determine the association of lymphadenectomy and intraoperative rupture on survival. <h3>Results:</h3> A total of 170 women with MOC were identified, of which 149 (88%) had apparent stage I disease upon presentation. Median age was 49, (IQR 33-58) and the majority presented with low-grade unilateral ovarian masses (grade 1; 71%) with median size of 20.5cm (IQR 16-28) and had a five-year OS of 88.9% (82.9-95.3%) and RFS of 82.7% (75.7-90.3%). Forty-eight (32%; N=149) patients had a pelvic and/or para-aortic lymphadenectomy, but only 1 patient with grade 2 disease was upstaged due to positive pelvic lymph nodes. Omentectomy was carried out in 128 (86%) patients, and 2 patients with grade 2 disease were upstaged due to microscopic omental disease (1.6%). Intraoperative rupture was documented in 52 cases (35%); these were more likely to have initial surgery performed by a non-gynecologic oncologist (48% vs 11%; p<0.001). At final pathology, 137 had stage I (92%), 5 stage II (3%), 6 stage III (4%) and 1 stage IV (1%) disease. Fifteen patients (10%) received adjuvant chemotherapy; there was no significant difference in the rate of adjuvant therapy between those with or without intraoperative rupture (p=0.39). There were 20 recurrences in the cohort (13%; 9 grade 1, 6 grade 2, 4 grade 3), with the vast majority peritoneal (95%). On multivariable analysis, after adjusting for age, final stage, and use of adjuvant chemotherapy, there was no significant association between intraoperative rupture with OS (HR 2.2 (0.6-8.0), p=0.25) or RFS (HR 1.3 (0.5-3.3), p=0.63) or lymphadenectomy with OS (HR 0.9 (0.3-2.8), p=0.90) or RFS (HR 1.2 (0.5-3.0), p=0.73). Advanced stage was the only factor that was significantly associated with survival. <h3>Conclusions:</h3> For women with apparent stage I MOC, a second operative procedure for systematic lymphadenectomy has low utility, as very few patients are upstaged and recurrence typically occurs in the peritoneum. Furthermore, intraoperative rupture does not independently confer a worse survival, and therefore these women do not benefit from adjuvant treatment based on rupture alone.

Definitive Chemoradiotherapy versus Radical Hysterectomy Followed by Tailored Adjuvant Therapy in Women with Early-Stage Cervical Cancer Presenting with Pelvic Lymph Node Metastasis on Pretreatment Evaluation: A Propensity Score Matching Analysis

Simple SummaryPelvic nodal involvement is frequently present in early-stage cervical cancer patients on pretreatment imaging studies. However, it is unclear whether radical chemoradiotherapy (CRT) or radical hysterectomy RH followed by tailored adjuvant radiotherapy is more appropriate in these patients. We compared oncological outcomes of up-front surgery followed by tailored adjuvant radiotherapy and definitive CRT in these patients. We found no differences in outcomes existed between definitive CRT and hysterectomy with tailored adjuvant radiotherapy. However, after surgery, 88.7% of patients required adjuvant radiotherapy. These findings suggest that definitive CRT can avoid unplanned tri-modality therapy without compromising oncologic outcomes.To compare the oncologic outcomes between chemoradiotherapy (CRT) and radical hysterectomy followed by tailored adjuvant therapy in patients with early cervical cancer presenting with pelvic lymph node metastasis. We retrospectively analyzed the medical records of women with early cervical cancer presenting with positive pelvic nodes identified on pretreatment imaging assessment. Propensity score matching was employed to control for the heterogeneity between two groups according to confounding factors. Overall survival, disease-free survival, and pattern of failure were compared between the two groups. A total of 262 patients were identified; among them, 67 received definitive CRT (group A), and 195 received hysterectomy (group B). Adjuvant therapy was administered to 88.7% of group B. There were no significant differences between group A and group B regarding the 5-year overall survival rates (89.2% vs. 89.0%) as well as disease-free survival rates (80.6% vs. 82.7%), and patterns of failure. Distant metastasis was the major failure pattern identified in both groups. In multivariate analysis, non-squamous histology was significantly associated with poorer overall survival. As there are no significant differences in 5-year OS, DFS, and patterns of failure, definitive CRT could avoid the combined modality therapy without compromising oncologic outcomes.

Clinical outcomes of patients with endometrioid epithelial ovarian cancer following surgical treatment.

Endometrioid epithelial ovarian cancer (EEOC) is rare, and its management poorly defined. We examined factors associated with 5-year progression-free survival (PFS) after surgery for EEOC. Retrospective study: treatment and outcomes of all EEOC patients undergoing initial surgery at, or presenting to, our institution within 3 months of initial surgery, 1/2002-9/2017. In total, 212 patients were identified. Median follow-up, 63.9 months (range, 0.7-192); median age at diagnosis, 52 years (range, 20-88); disease stage: I, n = 145 (68%); II, n = 47 (22%); III/IV, n = 20 (9%); FIGO grade: 1, 127 (60%); 2, 66 (31%); 3, 17 (8%); unknown, 2 (1%). One hundred twenty-eight (60%) had endometriosis; 75 (35%), synchronous endometrioid endometrial cancer (80%, IA); 101 (48%), complete surgical staging; 8 (5%), positive pelvic lymph nodes (LNs); 6 (4%), positive para-aortic LNs; 176 (97%), complete gross resection; 123 (60%), postoperative chemotherapy; 56(28%), no additional treatment. Five-year PFS, 83% (95% confidence interval [CI]: 76.6%-87.8%); 5-year overall survival (OS), 92.7% (95% CI: 87.7%-95.8%). Age, stage, and surgical staging were associated with improved 5-year PFS, and younger age at diagnosis with improved 5-year OS (p < 0.001). Chemotherapy did not improve 5-year PFS in IA/IB versus observation, but improved survival in IC (hazard ratio [HR]: 1.01, 95% CI: 0.22-4.59, p = 0.99; HR: 0.17, 95% CI: 0.04-0.7, p = 0.006). Age, stage, and full surgical staging were associated with improved 5-year PFS. Chemotherapy showed no benefit in IA/IB disease.

Comparison of Postoperative Adjuvant Chemotherapy and Concurrent Chemoradiotherapy for FIGO2018 Stage IIIC1 Cervical Cancer: A Retrospective Study.

Background and Objectives: In October 2018, the International Federation of Gynecology and Obstetrics (FIGO) revised its classification of advanced stages of cervical cancer. The main points of the classification are as follows: stage IIIC is newly established; pelvic lymph node metastasis is stage IIIC1; and para-aortic lymph node metastasis is stage IIIC2. Currently, in Japan, radical hysterectomy is performed in advanced stages IA2 to IIB of FIGO2014, and concurrent chemoradiotherapy (CCRT) is recommended for patients with positive lymph nodes. However, the efficacy of CCRT is not always satisfactory. The aim of this study was to compare postoperative adjuvant chemotherapy (CT) and postoperative CCRT in stage IIIC1 patients. Materials and Methods: Of the 40 patients who had undergone a radical hysterectomy at Iwate Medical University between January 2011 and December 2016 and were pathologically diagnosed as having positive pelvic lymph nodes, 21 patients in the adjuvant CT group and 19 patients in the postoperative CCRT group were compared. Results: The 5 year survival rates were 77.9% in the CT group and 74.7% in the CCRT group, with no significant difference. There was no significant difference in overall survival or progression-free survival between the two groups. There was no significant difference between CT and CCRT in postoperative adjuvant therapy in the new classification IIIC1 stage. Conclusions: The results of the prospective Japanese Gynecologic Oncology Group (JGOG) 1082 study are pending, but the present results suggest that CT may be a treatment option in rural areas where radiotherapy facilities are limited.

Oncologic outcomes in the era of modern radiation therapy using FIGO 2018 staging system for cervical cancer

BackgroundThe recently published ASTRO cervical cancer guidelines recommend the use of modern radiotherapy. Imaging is now incorporated in the updated FIGO 2018 staging with a new stage IIIC. This study aims to evaluate the oncologic outcomes and predictors of survival using FIGO 2018 staging in a cohort of patients treated in an era of high-precision image-guided radiotherapy. MethodsWe performed a retrospective cohort study of 216 adult cervical cancer patients treated with definitive chemoradiotherapy between 2010 and 2018. Eligible patients had non-metastatic cervical cancer treated at a single academic institution. All patients had pre-treatment MRI and CT/PET. Treatment protocol consisted of external beam intensity-modulated radiotherapy and 3D image-guided brachytherapy. Kaplan-Meier curves were used for survival analysis. Multivariate cox proportional-hazards model was performed to identify potential prognostic factors. ResultsMedian age at diagnosis was 50 and median BMI was 26.4 kg/m2. Median follow-up time was 44.3 months. Five-year overall survival (OS), disease-free survival and loco-regional disease-free survival rates were 76.8%, 68.5% and 82.6%, respectively. FIGO 2018 showed better OS discrimination compared to FIGO 2009 classification. OS was increasingly worse with positive pelvic and para-aortic nodes (p < 0.001). In a multivariate prediction model, performance status (p = 0.044) and FIGO 2018 classification (stage III p = 0.016; stage IVA p = 0.010) were predictors of mortality; FIGO 2018 classification (stage III p = 0.003; stage IVA p = 0.001) was a predictor of any recurrence; MRI tumor diameter (p ≤ 0.001) and nodal metastases (p = 0.024) were predictors of loco-regional recurrence. ConclusionsIntegration of state-of-the-art imaging in cervical cancer staging and in radiotherapy planning leads to good loco-regional control rates, however distant recurrence remains an important issue. FIGO 2018 staging better reflects patient prognosis, highlighting the need for new treatment strategies for stage IIIC cervical cancer.

Adjuvant Radiation Field Extent and Sites of Failure in Node Positive Endometrioid Endometrial Cancer

PurposeIn patients with node-positive endometrial cancer, adjuvant radiation therapy with chemotherapy decreases local-regional recurrence compared with chemotherapy alone. However, the optimal radiation field borders and extent of nodal coverage have not been well studied. In a multi-institutional cohort, survival outcomes and sites of failure were analyzed for patients with International Federation of Gynaecology and Obstetrics (FIGO) stage IIIC endometrioid endometrial cancer treated with pelvic radiation therapy (PRT) versus extended-field radiation therapy (EFRT), which encompassed high para-aortic lymph nodes. Methods and MaterialsIn a multi-institutional retrospective study, 143 patients with FIGO stage IIIC1 or IIIC2 endometrioid endometrial cancer treated with adjuvant radiation therapy from 2000 to 2016 were identified. Patient subgroups were classified by substage and radiation field extent: stage IIIC1 received EFRT, stage IIIC1 received PRT, and stage IIIC2 received EFRT. Recurrence-free survival (RFS), overall survival (OS), and out-of-field recurrence were calculated by the Kaplan-Meier method. Multivariate analysis was performed using the Cox proportional hazards model. Sites of failure were categorized as within or outside the radiation field. ResultsThe median follow-up was 59 months; 87% of patients received chemotherapy. The 5-year RFS and OS rates were 73% and 87%, respectively. By subgroup, 5-year RFS rates were 79% for stage IIIC1 EFRT, 73% for stage IIIC1 PRT, and 69% for stage IIIC2 EFRT (P = .4). On multivariate analysis, the recurrence risk was highest for stage IIIC2 EFRT, although this result was not statistically significant (adjusted hazard ratio, 2.0; P = .4). In-field vaginal and nodal recurrences were observed in 2 patients (1%) and 4 patients (3%), respectively. Of 78 patients with stage IIIC1 cancer treated with PRT, 5 (6%) had isolated para-aortic nodal relapse outside the radiation field; 3 were long-term survivors (more than 6 years after salvage therapy). For patients with para-aortic recurrence, 86% had lymphovascular invasion, 71% had myometrial invasion of ≥50%, and 57% had grade 3 disease. ConclusionsAdjuvant chemoradiation therapy resulted in excellent survival outcomes for patients with FIGO stage IIIC endometrioid endometrial cancer. For patients with positive pelvic nodes, isolated para-aortic relapse outside the PRT field was uncommon and amenable to salvage therapy.

Treatment strategy for locally advanced squamous cell cervical cancer with clinically positive pelvic lymph nodes metastasis.

To determine the optimal treatment for locally advanced squamous cell cervical cancer with clinical positive pelvic lymph nodes metastasis (cN1). We enrolled patients with squamous cell cervical cancer with 2008 FIGO stages IB, IIA, or IIB diagnosed with cN1, who were treated at Hyogo Cancer Center between April 2010 and December 2016. Patients with para-aortic lymph nodes metastasis were excluded. Of the 69 eligible patients, 24 underwent concurrent chemoradiotherapy (CCRT), 11 underwent radical hysterectomy with pelvic lymphadenectomy (RH) with or without adjuvant RT, and 34 underwent neoadjuvant chemotherapy (NAC) followed by RH as initial treatment. The regimens of NAC included dose-dense TC (paclitaxel 80 mg/m2 , days 1, 8, 15; and carboplatin at an area under the curve=6 on day 1, every 3 weeks) and dose-dense TP (paclitaxel 80 mg/m2 on days 1, 8, 15; and cisplatin 75 mg/m2 on day 1, every 3 weeks). The median observation period was 57 (12-107) months. The 5-year disease-free survival rates of the CCRT, RH, and NAC groups were 78.7%, 63.6%, and 88.2%, respectively (p=0.14). The 5-year overall survival rates of the CCRT, RH, and NAC groups were 78.6%, 70.1%, and 94.1%, respectively (p=0.11). We recommend avoiding RH as primary treatment for cN1 with locally advanced squamous cell cervical cancer. Although CCRT should be considered for cN1, further studies are required to determine if NAC followed by RH will serve as an effective option.

Positive lateral pelvic lymph nodes in low rectal cancer: should we change our practice now?

The role of lateral lymph node dissection (LLND) in the treatment of patients with low rectal cancer with enlarged lateral lymph nodes (LLN+) is under investigation. Enthusiasm for LLND stems from a perceived reduction in local recurrence (LR). We aimed to compare the LR rate for LLN+ patients with LLN- patients, treated with neoadjuvant chemoradiotherapy (nCRT) and surgery, in a hospital that does not perform LLND. A retrospective study of all patients with clinical stage 3 low rectal cancer who completed nCRT and surgery between 2008 and 2017 at Western Health was performed. Outcomes for LLN+ patients were compared with LLN- patients. The primary outcome was LR. Secondary outcomes included distant metastases, disease-free survival and overall survival. There were 110 patients treated for stage 3 low rectal cancer over 10 years. There was no significant difference in the LR rate, with one LR from 28 LLN+ patients and one LR from 82 LLN- patients (4% versus 1.2%, P=0.44). There were no significant differences in median disease-free survival (41 versus 52 months, P=0.19) or mean overall survival (62 versus 60 months, P=0.80). Of all patients studied, 21% developed distant metastases. LR after nCRT and surgery in patients with stage 3 rectal cancer is rare, irrespective of lateral pelvic node status. These data, along with the uncertain benefit and known risks of LLND, supports the continued use of standard therapy in these patients. Strategies to address distant failure in these patients should be explored.

Prospective observational study evaluating acute and delayed treatment related toxicities of prophylactic extended field volumetric modulated arc therapy with concurrent cisplatin in cervical cancer patients with pelvic lymph node metastasis.

To evaluate the treatment related acute and delayed toxicities of extended field Volumetric modulated arc therapy (VMAT) with concurrent chemotherapy in patients of locally advanced cervical cancer with pelvic lymph nodes. From 2014 to 2016, 15 patients of locally advanced cervical cancer with Fluoro-deoxyglucose positron emission tomography (FDG-PET) positive pelvic lymph nodes were treated with extended field Simultaneous integrated boost (SIB)-VMAT 45 Gy/55 Gy/25#/5weeks and concurrent cisplatin. Acute toxicities were documented according to common terminology criteria for adverse events version 4 (CTCAE v.4). Dose volume parameters and patient characteristics were analyzed for association with toxicities. Median age of patients at diagnosis was 48 years. 40% (6 patients) were stage IIB & 60% (9 patients) were stage IIIB. Median number of involved pelvic lymph nodes was 2 (range, 1-4), commonest location was external iliac lymph node region (86%). Median number of concurrent chemotherapy cycles received was five. Treatment was well tolerated and there were no grade ≥ 3 acute toxicities. Commonest acute toxicities observed were vomiting (≥grade2 -13.3%) followed by & nausea (grade ≥ 2 in 6%) and were associated with volume of bowel bag receiving 45 Gy. Constitutional symptoms (≥grade 2) were observed in 6% patients and had no dosimetric associations. At a median follow up of 43 months, delayed ≥ grade1, 2, 3 toxicity were observed in 80%, 0%, and 0% respectively with diarrhea being the commonest. Prophylactic para aortic extended field VMAT with concurrent chemotherapy for locally advanced cervical cancer is well tolerated with acceptable acute toxicity profile. Significant grade 3 acute/delayed toxicities were not observed in this cohort of patients.

Simultaneous Integrated Boost Intensity-Modulated Radiation Therapy Can Benefit the Locally Advanced Rectal Cancer Patients With Clinically Positive Lateral Pelvic Lymph Node.

Background and PurposeThe optimal treatment modality for clinically positive lateral pelvic lymph node (LPLN) from locally advanced rectal cancer (LARC) is unknown. Thus, we aimed to analyze the optimal radiotherapy dose for clinically positive LPLN from LARC.Materials and MethodsWe retrospectively evaluated distal LARC (i.e., within 8 cm from the anal verge) patients with clinically positive LPLN (i.e., ≥7 mm in the short axis). They were divided into two groups based on whether or not they received simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT)–based chemoradiotherapy. The total radiotherapy dose on LPLN were 56-60Gy for SIB-IMRT group and 41.8Gy for non-SIB-IMRT group. The clinical parameters and regrowth rate of LPLN were then compared between the two groups.ResultsA total of 151 patients were evaluated, and 83 and 68 patients were classified to the SIB-IMRT and non-SIB-IMRT group, respectively. The median follow-up period was 22.6 months, and the 2-year LPLN regrowth rate was significantly different between the SIB-IMRT group and the non-SIB-IMRT group (0% vs 10.8%, P=0.024). Further, SIB-IMRT yielded a significantly lower 2-year LPLN regrowth rate in patients whose LPLN measured ≥8 mm in the short axis (0% vs. 15.9%, P=0.019) or ≥10 mm in the long axis (0% vs. 17.6%, P=0.024) compared to patients who were in non-SIB-IMRT group. Meanwhile, there was no significant difference in grade II radiation-related toxicity (30.1% vs. 39.1%, P=0.217) and surgical complications (21.8% vs. 12.2%, P=0.198) between the two groups.ConclusionSIB-IMRT–based neoadjuvant chemoradiotherapy is beneficial for eliminating clinically positive LPLN from LARC without increasing the incidence of radiotherapy-related toxicity and surgical complications, and patients with larger LPLN may gain benefit from this technique.

Association between percentage of positive biopsy cores and risk of pelvic lymph node involvement in prostate cancer.

205 Background: Commonly used tools for predicting the risk of pelvic lymph node involvement (LNI) in prostate cancer often do not incorporate information on the percentage of positive biopsy cores (PPB). To better inform the use of elective nodal irradiation in the definitive treatment of prostate cancer, we examined the association between PPB and risk of pathologic pelvic LNI in men with prostate cancer who underwent radical prostatectomy (RP). Methods: We identified 109,577 men from the National Cancer Database who were diagnosed in 2010-2015 with cN0M0 prostate cancer, had 6-24 cores sampled at biopsy, and underwent RP with pathologic nodal evaluation. Multivariable logistic regression was used to examine the association between PPB and the likelihood of having ≥1 positive pelvic lymph node, adjusting for other known clinicopathologic prognostic variables. Results: Overall, 4.0% (4,340) of the cohort was found to have pelvic LNI at the time of RP. Higher PPB was associated with an increased risk of pelvic LNI (adjusted odds ratio [AOR] 1.75 for 25.1-50.0% PPB, 2.63 for 50.1-75.0% PPB, and 4.49 for 75.1-100.0% PPB vs. ≤25.0% PPB, all P&lt;0.001). Notably, men with Gleason 8 disease and ≤25.0% PPB only had a 3.6% risk of pelvic LNI, whereas men with Gleason 9-10 disease and 75.1-100.0% PPB had a 32.6% risk (Table). Other factors associated with the likelihood of pelvic LNI included a higher biopsy Gleason score (AOR 1.43 for Gleason 8 and 2.84 for Gleason 9-10 vs. Gleason 4+3, both P&lt;0.001), more advanced clinical tumor stage (AOR 1.48 for cT2, 1.97 for cT3, and 3.87 for cT4 vs. cT1, all P&lt;0.001), and a higher PSA (AOR 1.90 for 10.0-19.9 ng/mL, 2.40 for 20.0-39.9 ng/mL, and 2.60 for ≥40.0 ng/mL vs. &lt;10.0 ng/mL, all P&lt;0.001), but not more advanced age (AOR 0.98 for &gt;62 years [median] vs. ≤62 years, P=0.59) or black vs. white race (AOR 0.99, P=0.92). Conclusions: There was a statistically significant and clinically relevant association between increasing PPB and a higher risk of pelvic LNI. As the ongoing RTOG 0924 randomized trial matures, clinicians should consider incorporating information on PPB in determining which patients with prostate cancer may benefit from receiving radiation therapy to the pelvic lymph nodes. [Table: see text]

Stereotactic Body Radiotherapy for High-Risk Prostate Cancer: A Systematic Review.

Simple SummaryStereotactic body radiotherapy, i.e., high-precision radiotherapy delivering high doses within a few treatment sessions, is a very convenient treatment option, which has been shown to be effective and well tolerated in prostate cancer patients with low- or intermediate-risk profiles. This review summarizes the available data and analyzes, whether this modern treatment may routinely be offered to prostate cancer patients with a high-risk profile.Background: Radiotherapy (RT) is an established, potentially curative treatment option for all risk constellations of localized prostate cancer (PCA). Androgen deprivation therapy (ADT) and dose-escalated RT can further improve outcome in high-risk (HR) PCA. In recent years, shorter RT schedules based on hypofractionated RT have shown equal outcome. Stereotactic body radiotherapy (SBRT) is a highly conformal RT technique enabling ultra-hypofractionation which has been shown to be safe and efficient in patients with low- and intermediate-risk PCA. There is a paucity of data on the role of SBRT in HR PCA. In particular, the need for pelvic elective nodal irradiation (ENI) needs to be addressed. Therefore, we conducted a systematic review to analyze the available data on observed toxicities, ADT prescription practice, and oncological outcome to shed more light on the value of SBRT in HR PCA. Methods: We searched the PubMed and Embase electronic databases for the terms “prostate cancer” AND “stereotactic” AND “radiotherapy” in June 2020. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Results: After a rigorous selection process, we identified 18 individual studies meeting all selection criteria for further analyses. Five additional studies were included because their content was judged as relevant. Three trials have reported on prostate SBRT including pelvic nodes; 2 with ENI and 1 with positive pelvic nodes only. The remaining studies investigated SBRT of the prostate only. Grade 2+ acute genitourinary (GU) toxicity was between 12% and 46.7% in the studies investigating pelvic nodes irradiation and ranged from 0% to 89% in the prostate only studies. Grade 2+ chronic GU toxicity was between 7% and 60% vs. 2% and 56.7%. Acute gastrointestinal (GI) grade 2+ toxicity was between 0% to 4% and 0% to 18% for studies with and without pelvic nodes irradiation, respectively. Chronic GI grade 2+ toxicity rates were between 4% and 50.1% vs. 0% and 40%. SBRT of prostate and positive pelvic nodes only showed similar toxicity rates as SBRT for the prostate only. Among the trials that reported on ADT use, the majority of HR PCA patients underwent ADT for at least 2 months; mostly neoadjuvant and concurrent. Biochemical control rates ranged from 82% to 100% after 2 years and 56% to 100% after 3 years. Only a few studies reported longer follow-up data. Conclusion: At this point, SBRT with or without pelvic ENI cannot be considered the standard of care in HR PCA, due to missing level 1 evidence. Treatment may be offered to selected patients at specialized centers with access to high-precision RT. While concomitant ADT is the current standard of care, the necessary duration of ADT in combination with SBRT remains unclear. Ideally, all eligible patients should be enrolled in clinical trials.

Role of radical hysterectomy in patients with early-stage high-grade neuroendocrine cervical carcinoma: a NeCTuR study

ObjectivePatients with early-stage, high-grade neuroendocrine cervical carcinoma typically undergo radical hysterectomy with pelvic lymphadenectomy followed by adjuvant radiotherapy and/or chemotherapy. To explore the role of radical surgery in patients with...