Extended-field Radiotherapy Research Articles

168 A study on 3 types of patient immobilisation gadgets with IGRT for extended-field gynaecological RT

168 A study on 3 types of patient immobilisation gadgets with IGRT for extended-field gynaecological RT

139 Feasibility of Extended Field Radiation using Volumetric Modulated Arc Therapy in Prostate Cancer

139 Feasibility of Extended Field Radiation using Volumetric Modulated Arc Therapy in Prostate Cancer

Pegylated recombinant human granulocyte colony-stimulating factor for primary prophylaxis of neutropenia in patients with cervical cancer receiving concurrent chemoradiotherapy: a prospective study

BackgroundThis study aimed to investigate the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) for primary prophylaxis of neutropenia in patients with cervical cancer receiving concurrent chemoradiotherapy.MethodsIn this prospective, single-center, single-arm study, we enrolled patients (18–70 years) with 2018 International Federation of Gynecology and Obstetrics (FIGO) stage IIIC1r-IVA and IVB (distant metastasis only with inguinal lymph node metastasis) cervical cancer. Eligible patients should have normal function of the bone marrow (absolute neutrophil count (ANC) ≥ 2.0 × 109/L) and adequate hepatic and renal functions. Key exclusion criteria included: previous chemotherapy and/or radiotherapy; a history of bone marrow dysplasia or other hematopoietic abnormalities. All patients underwent radical radiotherapy (pelvic radiotherapy or extended-field irradiation) plus brachytherapy. The chemotherapy regimen included four cycles of 3-weekly paclitaxel and cisplatin. PEG-rhG-CSF was administered 48–72 h after each treatment cycle. Salvage granulocyte colony-stimulating factor (G-CSF) was only permitted in certain circumstances. The primary endpoint was the incidence of grade 3–4 neutropenia. The secondary endpoints included frequency of febrile neutropenia (FN), chemotherapy completion rate in cycles 2–4, time to complete radiotherapy, and safety.ResultsOverall, 52 patients were enrolled in this study from July 2019 to October 2020. The incidence of grade 3–4 neutropenia was 28.8%, with an average duration of grade 3–4 neutropenia persistence of 3.85 days (1–7 days). The incidence rate of FN was 3.8%. The chemotherapy completion rate was 94.2%, 82.7%, and 75.0% for cycles 2–4, respectively. The incidences of grade 3–4 neutropenia for cycles 1–4 were 9.6% (5/52), 8.2% (4/49), 14.0% (6/43), and 2.6% (1/39), respectively. All patients completed radiotherapy within 8 weeks (median, 48 days; range: 41–56 days), except one patient who withdrew consent and did not receive radiotherapy. Severe non-hematologic toxicity was not observed in any patient.ConclusionPEG-rhG-CSF is an effective and safe prophylactic treatment for neutropenia in patients with cervical cancer undergoing concurrent chemoradiotherapy.Trial registrationChinese Clinical Trial Registry, ChiCTR1900024494. Date of Registration:13/July/2019.

Pelvic Bone Marrow Sparing Intensity Modulated Radiation Therapy Reduces the Bone Mineral Density Loss of Patients With Cervical Cancer

PurposeTo test the efficacy and feasibility of pelvic bone marrow sparing intensity modulated radiotherapy (PBMS-IMRT) in reducing bone density loss for patients with cervical cancer undergoing pelvic radiotherapy (RT). Methods and MaterialsNon-surgical cervical cancer patients with Stage Ib2–IIIc cancer were randomly allocated into the PBMS group or the control group. The PBMS group additionally received PBM dose constraint. Computed tomography (CT) imaging sets were acquired at baseline and at 1, 3, 6, 9, and 12 months after treatment. Radiation dose and Hounsfield unit (HU) were registered. Bone density loss rates and fracture events at different follow-up time points were recorded. ResultsData from 90 patients in the PBMS group and 86 patients in the control group were used for statistical analysis, which included 30 and 26 patients with extended-field RT (EFR), respectively. The median follow-up for all patients was 12 months. Compared to baseline, the bone density of all bones at the last follow-up had decreased by 43% and 53% in the PBMS and control groups, respectively, with the most significant decline at 1 month after treatment. Although patients without extended-field radiation received minimal irradiation in the upper lumbar spine, a 22.33% decrease in bone density was detected. In the group of patients with EFR, the decrease was 51.18% (P < 0.01). Lumbar or pelvic fracture incidence rates of patients in the PBMS and control groups were 7.8% and 12.79%, respectively. Among the dosimetric parameters, mean dose had the strongest correlation with bone density loss. ConclusionIn patients undergoing pelvic RT, the loss of bone density can begin to appear early after RT, and it can occur either inside or outside of the irradiation field. Results of this study showed that PBMS-IMRT reduced bone mineral density loss compared with IMRT alone.

Outcomes of minimal access retroperitoneal para-aortic lymphadenectomy in patients with locally advanced cervical cancer

Background To evaluate outcomes of laparoscopic retroperitoneal para-aortic lymphadenectomy for stage 1b3-3b cervical cancer. Methods Pathology databases searched for all para-aortic lymphadenectomy cases 2005–2016. Descriptive statistics were used to analyse baseline characteristics, cox models for treatment affect after accounting for variables, and Kaplan Meier curves for survival (STATA v15). Results 191 patients had 1b3-3b cervical cancer of which 110 patients had Para-aortic lymphadenectomy. 8 (7.3%) patients stage 1b3, 82 (74.6%) stage 2b, and 20 (18.1%) stage 3b cervical cancer. Mean lymph node count 11.7 (SD7.6). The intra-operative and post-operative 30 day complication rates were 8.8% (CI: 4.3%, 15.7%) and 5.3% (CI: 1.9%, 11.2%) respectively. Para-aortic nodes were apparently positive on CT/MRI in 5/110 (5%) cases. Cancer was found in 10 (8.9%, CI: 4.3%, 15.7%) cases on histology, all received extended field radiotherapy. Only 2 were identified on pre-operative CT/MRI imaging. 3 of 10 suspected node-positive cases on CT/MRI had negative histology. Para-aortic lymphadenectomy led to alteration in staging and radiotherapy management in 8 (8%, CI: 3.7%, 14.6%) patients. Mean overall survival 42.81 months (SD = 31.79 months). Survival was significantly higher for women undergoing PAN (50.57 (SD 30.7) months) compared to those who didn’t (31.27 (SD 32.5) months) Conclusion Laparoscopic retroperitoneal para-aortic lymphadenectomy is an acceptable procedure which can guide treatment in women with locally advanced cervical cancer.

A Single-center Experience of Radiotherapy in Pediatric Ewing Sarcoma/Primitive Neuroectodermal Tumor of the Chest Wall.

To evaluate the treatment results, prognostic parameters, and treatment-related toxicity in patients with Ewing sarcoma (ES)/primitive neuroectodermal tumor (PNET) of the chest wall who underwent surgery, chemotherapy, and radiotherapy (RT) in a tertiary referral center. The data of 24 patients under 18 years of age with a histologic diagnosis of ES/PNET in the chest wall that received RT in our department between February 2003 and July 2020 were retrospectively evaluated. RT was applied to the primary site±whole involved chest wall and to the whole lung in patients with lung metastasis. The median age was 8.5 years (range: 1.5 to 17y), 15 (63%) patients were female and 9 were male (37%). The tumor localization was extrathoracic in 18 (75%) and intrathoracic in 6 (25%) patients. Mediastinal lymph node and distant metastasis (DM) was present in 5 (21%) and 4 (16%) cases at diagnosis, respectively. The median follow-up after RT was 47 months (range: 11 to 162mo). The 2-year and 5-year overall survival, event-free survival, local recurrence-free survival, and pleural recurrence-free survival were 83% and 48%, 48% and 42%, 74% and 48%, and 61% and 52%, respectively. The overall local control rate was 83% and the pleural control rate was 67%. RT was well tolerated, with 1 case of grade 3 acute dermatitis and 1 case of grade 3 subacute radiation pneumonitis. Late toxicity was observed in 3 (13%) cases. Long-term survival can be achieved with extended-field RT even in patients with ES/PNET of the chest wall with DM. The low toxicity rates allow us to draw the conclusion that RT with modern techniques is an effective and safe treatment modality for these patients.

Comparative Analysis of Oncologic Outcomes in Patients with Squamous Cell Carcinoma of the Uterine Cervix with High-Risk Features for Para-Aortic Recurrence: Prophylactic Extended-Field versus Pelvic Chemoradiotherapy.

To compare the oncologic outcomes of prophylactic extended-field radiation therapy (EFRT) and whole pelvic radiation therapy (WPRT) in cervical patients at high risk of para-aortic lymph node (PALN) recurrence. From July 1999 to May 2022, a total of 115 patients with cervical cancer and high-risk features of PALN recurrence based on tumor markers, positive LNs and extensive parametrial invasion were retrospectively analyzed. All patients had received EFRT or WPRT at a dose of 39.6-45 Gy and concurrent chemotherapy. In EFRT, coverage was extended to include the para-aortic region below the level of the left renal vein or T12. Twenty-eight and 87 patients underwent EFRT and WPRT, respectively. For patients who survived, the median follow-up time was 60.8 months (range 9.2-131.6 months) in the EFRT group and 115.9 months (range 16.9-212.1 months) in the WPRT group. The 5-year overall survival (OS) and pelvic, extrapelvic and PALN recurrence rates were 87.7% vs 60.8% (p=0.019), 10.9% vs 25.3% (p=0.119), 18.1% vs 45.8% (p=0.011), and 0% vs 30.4% (p=0.005), respectively, between the EFRT and WPRT groups. Multivariate analysis revealed that EFRT and 2018 FIGO stage IV disease status were significant predictors ofOS and extrapelvic recurrence. Compared to WPRT, EFRT significantly improved OS and reduced extrapelvic and PALN recurrence in patients with cervical cancer with high-risk recurrence features.

Evaluation of the toxicity of prophylactic extended-field radiation therapy with volumetric modulated arc therapy in combination with concomitant chemoradiotherapy in patients with locally advanced stage IIIC1r cervical cancer according to the 2018 FIGO classification.

To evaluate the toxicity of prophylactic extended-field radiation therapy (EFRT) combined with volumetric modulated arc therapy (VMAT) in combination with cisplatin chemotherapy for locally advanced stage IIIC1r cervical cancer [2018 International Federation of Gynecology and Obstetrics (FIGO)]. Thirty patients with stage IIIC1r cervical cancer were treated with EFRT combined with concurrent cisplatin. Acute toxicities were evaluated according to the common terminology criteria for adverse events (CTCAE v.5). Delayed toxicities were evaluated according to the classification criteria of radiation damage toxicity of the Radiation Therapy Oncology Group (RTOG). The efficacy of the regimens was evaluated using response evaluation criteria in solid tumors (RECIST v1.1). Spearman correlation was used to analyze the correlation between acute gastrointestinal toxicity (nausea) and the small bowel V45. Predictive value analysis was performed using a receiver operating characteristic (ROC) curve. There were no grade ≥ 3 acute toxicities. The most common acute toxicity observed was nausea (grade 2 in 40%), which was positively correlated with the volume of the small intestine receiving 45 Gy. When the V45 of the small intestine was > 83.2 cc, the risk of grade 2 acute upper digestive tract toxicity (nausea) increased. The major late toxicities had the following distributions: Grade 1 diarrhea, 36.7%; Grade 1 abdominal pain, 13.3%; and Grade 1 radiation cystitis. No grade ≥ 2 late toxicities were observed. Treatment of locally advanced stage IIIC1r cervical cancer with EFRT combined with VMAT and concurrent cisplatin chemotherapy was well tolerated, and the acute toxicity profile was acceptable. Significant grade 3 acute/delayed toxicities were not observed.

Treatment Strategies Guided by [18F]FDG-PET/CT in Patients with Locally Advanced Cervical Cancer and [18F]FDG-Positive Lymph Nodes.

Modern treatment guidelines for women with advanced cervical cancer recommend staging using 2-deoxy-2-[18F]fluoro-D-glucose positron emission computed tomography ([18F]FDG-PET/CT). However, the risk of false-positive nodes and therapy-related adverse events requires caution in treatment planning. Using data from the Netherlands Cancer Registry (NCR), we estimated the impact of [18F]FDG-PET/CT on treatment management in women with locally advanced cervical cancer, i.e., on nodal boosting, field extension, and/or debulking in cases of suspected lymph nodes. Women diagnosed between 2009 and 2017, who received chemoradiotherapy for International Federation of Gynaecology and Obstetrics (2009) stage IB2, IIA2-IVB cervical cancer with an [18F]FDG-positive node, were retrospectively selected from the NCR database. Patients with pathological nodal examination before treatment were excluded. The frequency of nodal boosting, extended-field radiotherapy, and debulking procedures applied to patients with [18F]FDG-positive lymph nodes was evaluated. Among the 434 eligible patients with [18F]FDG-positive nodes, 380 (88%) received interventions targeting these lymph nodes: 84% of these 380 patients received nodal boosting, 78% extended-field radiotherapy, and 12% debulking surgery. [18F]FDG-positive nodes in patients receiving these treatments were more likely to be classified as suspicious than inconclusive (p = 0.009), located in the para-aortic region (p < 0.001), and larger (p < 0.001) than in patients who did not receive these treatments. While existing guidelines advocate [18F]FDG-PET/CT-guided treatment planning for the management of advanced cervical cancer, this study highlights that not all cases of [18F]FDG-positive nodes received an intervention, possibly due to the risk of false-positive results. Improvement of nodal staging may reduce suboptimal treatment planning.

Enhancing quality assurance in radiotherapy for gynaecological cancers: implementation of an on-demand peer review process.

Ensuring high-quality radiotherapy requires peer-reviewing target volumes. The Royal College of Radiologists recommends peer review specifically for individual target volumes in cases of gynaecological cancers. This study presents the outcomes of implementing an on-demand peer review system for gynaecological cancers within our institute. The peer review process was planned for gynaecological cancer cases intended for curative radiotherapy. After junior clinical oncologists (COs) completed the segmentation, two senior COs specializing in gynaecological cancers conducted the peer review. All peer review outcomes were recorded prospectively. The audit process compliance, the proportion of patients requiring major and minor modifications in target volumes, the direction of changes, and the factors influencing these changes were reported. A total of 230 patients were eligible, and out of these, 204 (88.3%) patients underwent at least one peer review. Among the patients, 108 required major modifications in their target volumes. P-charts revealed a stabilization in the need for major modifications at the end of three months, indicating that 38.2% and 28% of patients still required major modifications for the nodal and primary CTV, respectively. Multivariable analysis demonstrated that major modifications were associated with the use of extended field radiotherapy and radical radiation in non-cervical primary cases. An on-demand peer review system was feasible and resulted in clinically meaningful, major modifications in the target volumes for 53% of patients. Gynaecological cancers require ongoing peer review to ensure quality of care in radiotherapy. A flexible on-demand system not only ensures that patient treatment start is not delayed but also has an important educational role for junior trainees.

Outcome and toxicity of chemoradiation using volumetric modulated arc therapy followed by 3D image-guided brachytherapy for cervical cancer: Vietnam National Cancer Hospital experience.

Volumetric modulated arc therapy (VMAT) and 3D image-guided brachytherapy (3D-IGBT) have recently been introduced in Vietnam for the treatment of locally advanced cervical cancer. This study aims to assess the outcomes and toxicities of chemoradiation using VMAT followed by 3D-IGBT in Vietnamese cervical cancer patients. A prospective interventional study on 72 patients with 2018 International Federation of Gynecology and Obstetrics (FIGO) stage IB3-IIIC2 disease who underwent concurrent chemoradiation using VMAT, followed by 3D-IGBT according to EMBRACE-II protocol. Primary endpoints were locoregional control; secondary endpoints were systemic control and toxicity. Median body volume received 43 Gy was 1589.1 cm3 (range 1214.8-2574.8). Median high-risk clinical target volume (CTV-HR) was 18.8 cm3 (range 8.6-61.2) with a median dose to 90% (D90) of CTV-HR of 90.6 Gy (range 86.8-99.6). Mean doses to 2cc (D2cc) of bladder, rectum, and sigmoid were 75.8, 55.2, and 62.1 Gy, respectively. At median 19-month follow-up (range 12-25), locoregional control and systemic control were 95.8% and 81.9%, respectively. Systemic control was the lowest in N2 disease (54.5%). Grade ≥ 3 acute toxicities were less than 10%, except neutropenia (31.9%). Extended-field radiation increased significantly nausea, fatigue, and thrombocytopenia. No grade ≥ 3 proctitis or cystitis; 8.3% had grade 3 vaginal stenosis. VMAT-based chemoradiation therapy followed by 3D-IGBT achieved high locoregional control with manageable toxicities in locally advanced cervical cancer. Systemic control correlated with disease stage.

Study of long-term effects of pelvic radiotherapy on the function of bone marrow in recurrent cervical cancer patients.

Purpose: To study the effects of prior pelvic radiotherapy on bone marrow suppression in recurrent cervical cancer patients during chemotherapy. Methods and materials: The cases of 129 patients with recurrent cervical cancer were reviewed, of which 77 patients had pelvic radiotherapy history and another 52 patients with no pelvic radiotherapy history were used as control group. All patients received a chemotherapy regimen of paclitaxel combined with carboplatin (TC) per 21 days for 5-6 times. Hematologic toxicity, including count of red blood cell, white blood cell and neutrophil cell and platelet, was defined by using Common Terminology Criteria for Adverse Events (version 4.0). The relationship between age, body mass index, disease free survival, pathological types, FIGO stages, radiotherapy methods and the degree of bone marrow suppression during chemotherapy was statistically analyzed, respectively, for all recurrent cervical cancer patients. Results: Among 77 patients with previous radiotherapy history, 73 recurrent patients (94.8%) had bone marrow suppression followed by chemotherapy. Recurrent cervical cancer patients without prior radiotherapy (n=52) showed a lower risk of bone marrow suppression followed by chemotherapy (n=39, 75.0%, P < 0.05). The probability of severe bone marrow suppression (grade III-IV) after chemotherapy in recurrent cervical patients with or without history of radiotherapy was 41.6% and 13.5%, respectively (P < 0.05). In univariate analysis, radiotherapy methods were associated with the incidence of grade III-IV bone marrow suppression in recurrent cervical cancer patients (P=0.005). In multivariate analysis, radiotherapy methods and extended-field radiotherapy were the risk factor of grade III-IV bone marrow suppression (χ2=16.975, P=0.001). No significant differences in the counts of white blood cell, hemoglobin and platelet were observed before chemotherapy at relapse between patients with and without prior radiotherapy. Reduction of white blood cell counts, absolute value of neutrophil cell and platelet counts composited majority type of grade III and IV bone marrow suppression. Conclusions: The prior pelvic radiotherapy significantly increased the incidence of bone marrow suppression during chemotherapy in recurrent cervical cancer patients. When treating recurrent cervical cancer patients with chemotherapy who had prior radiotherapy, especially for those experienced external beam radiation therapy, essential attention and timely intervention are recommended to ensure completion of chemotherapy and clinical efficacy.

Prognostic Importance of Uterine Body Invasion in Para-Aortic Lymph Node Recurrence in Patients with Cervical Carcinoma after Pelvic Radiotherapy

This study aimed to evaluate the correlation between the extent of uterine body invasion and para-aortic lymph node (PALN) recurrence in patients with cervical carcinoma who received pelvic radiotherapy. The data of 185 patients diagnosed with cervical carcinoma, initial stage IB to IVA without para-aortic lymph node metastasis, according to the FIGO 2009 Stage System, and treated between January 2011 and December 2016 were retrospectively analyzed. With using pelvic MRI with contrast, the extent of uterine body invasion was assessed and categorized into three types: non-uterine invasion, endocervical invasion, and invasion into the uterine body. Non-uterine invasion, by definition, referred to tumor located at the outer orifice of the cervix or ectocervix, while endocervical invasion referred to tumor invasion up to the endocervical canal, and the uterine body invasion referred to cervical carcinoma invading the uterine cavity from the squamocolumnar junction (SCJ) transformation zone. Definitive or adjuvant pelvic radiotherapy was given to the 185 patients, all of whom did not receive extended-field radiotherapy. The major result of PALN recurrence, defined as a short axial diameter of lymph node greater than 1cm, was diagnosed through computed tomography, pelvic MRI, or PET-CT. The actuarial rates of PALN recurrence were analyzed using Kaplan-Meier curves, and Cox regression models were used for multivariate analyses. There were 122 (65.9%), 37 (20.0%), and 26 (14.1%) patients with non-uterine invasion, endocervical invasion, and invasion into the uterine body, respectively. The 5-year PALN recurrence rates were 7.8% in the non-uterine invasion group, 13.1% in the endocervical invasion group, and 21.1% in the uterine body invasion group (p = 0.009), after a median follow-up of 65.5 months. The multivariate analysis revealed that uterine body invasion was the only independent factor of PALN recurrence (p = 0.004). Factors such as initial pelvic lymphadenopathy (p = 0.645), initial SCC-Ag level (p = 0.200), non-squamous cell carcinoma (p = 0.882), and FIGO stage III-IVA (p = 0.289) were not significant factors of PALN recurrence. This study demonstrates that cervical cancer patients with uterine body invasion have a higher risk of PALN recurrence following pelvic radiotherapy. Intensive follow-up schedules are recommended for these patients. Extended-field radiotherapy may be considered in cervical cancer patients with uterine body invasion to reduce PALN recurrence.

Prophylactic Para-Aortic Extended Field Irradiation with Concurrent Chemotherapy for FIGO Stage IIIC1 Cervical Cancer Using Intensity Modulated Radiotherapy Technique: Acute Toxicity and Dosimetric Assessment

To evaluate the efficacy of P - PART with concurrent chemotherapy in LACC with the use of intensity modulated radiotherapy technique (IMRT). Our Primary endpoint was to assess acute toxicities and secondary endpoint was to assess loco-regional control (LRC), disease free-survival (DFS), para-aortic recurrence free survival (PA-RFS). A total of 30 patients of squamous cell carcinoma of cervix with stage IIIC1 (FIGO-2018) were recruited in this prospective, single arm interventional phase II study between January 2021 to September 2022. 18FDG-PET CT was performed and those with positive PALN were excluded. IMRT was used to deliver a dose of 50 Gy in 25 fractions to whole pelvis and PALN chain below renal hilum till aortic bifurcation received 45 Gy in 25 fractions. Concurrent cisplatin was administered weekly at 40 mg/m2 during radiation. On completion of external beam radiotherapy, high dose rate intracavitary brachytherapy was given at 7 Gy per fraction in 3 fractions prescribed to HR-CTV. Acute toxicities were assessed using CTCAE version 5.0. Median age was 50 years (37-66 years). All patients had completed treatment as per protocol. All patients had positive pelvic nodes with the maximum nodal short axis dimension of 14 mm (10-18 mm). All patients had positive internal iliac group of LNs, only 2(6.6%) patients had positive common iliac group of Ln. Median number of concurrent cisplatin cycles given were 5 (3-5 cycle). Median overall treatment time was 56 days (52-63 days) and median follow up was 15 months (3-22 month). Median cumulative dose to HR-CTV was 84.3Gy (Range:79.2-86.9Gy). Cumulative median EQD2 to 2cc of bladder and rectum were 69.11Gy (Range:59.17 - 80.07 Gy) and 64.6 Gy (Range: 60.1-66.3Gy) respectively. 7(23.3%) patients having grade 3 diarrhea and 2(6.67%) patients had grade 3 anemia while no significant genitourinary or other toxicities were noted. Patient characteristics, dosimetric data are described in Table-1. All patients underwent clinical and radiological assessment at the time of last follow up with one (3.33%) patient experiencing local failure at 9 months of follow up, hence crude LRC rate is 96.6%, DFS is 13.5 months (5-22 months) and PA-RFS is 16 months (8-23 months) till last date of follow up. Prophylactic EFRT with concurrent chemotherapy using IMRT technique yielded excellent short term clinical outcomes with acceptable toxicity profiles. Longer follow up will elucidate late toxicity and long-term clinical outcomes.

Concurrent intensity-modulated radiation therapy and chemotherapy plus nimotuzumab for locally advanced cervical squamous cell cancer: A long-term follow-up result

The study aimed to evaluate the safety and efficacy of concurrent intensity-modulated radiation therapy (IMRT) and chemotherapy plus nimotuzumab for the treatment of locally advanced cervical squamous cell cancer (LACSCC). From December 2013 to March 2017, 34 patients with stages IB2&amp;ndash;IVA (FIGO 2009) cervical squamous cell cancer were enrolled and received concurrent chemoradiotherapy plus nimotuzumab. The prescription radiation dose was 50.4 Gy/28 F on the pelvic field with or without extended-field radiation. An additional 30&amp;ndash;36 Gy to Point A was delivered with high-dose-rate brachytherapy. Cisplatin 40 mg/m2 and nimotuzumab 200 mg were infused intravenously weekly. The main and secondary outcome measures were toxicity evaluated using common terminology criteria for adverse events 4.03. and the outcome evaluated using response evaluation criteria in solid tumors 1.1, respectively. The median follow-up duration was 66 months (13 &amp;ndash; 98 months). All patients received 6 times of IMRT, brachytherapy, and nimotuzumab. Among them, 24 received six cycles of chemotherapy, while 11 received 4&amp;ndash;5 cycles. No life-threatening toxicity was found. The incidence of acute Grade 3 bone marrow depression was 52.9% (18/34), and Grade 3 gastrointestinal tract reaction was 8.8% (3/34). The incidence of late toxicities was 58.8% (20/34), including vaginal-rectal fistula, intestinal obstruction, rectal hemorrhage, hematuria, vaginal stenosis, and paresthesia. About 90% of those were Grades 1&amp;ndash;2. Complete response was achieved in 33 cases (97.1%). The 3-year disease-free survival, local progression-free survival (LPFS), and overall survival rates were 79.4%, 91.2%, and 82.4%, respectively. The corresponding 5-year values were 79.4%, 91.2%, and 79.3%. In conclusion, concurrent IMRT and chemotherapy plus nimotuzumab may represent a well-tolerated and effective treatment regimen in patients with LACSCC.

Intensity-modulated radiation therapy with the central shielding technique for patients with uterine cervical cancer

Abstract We aimed to examine outcomes and toxicities of intensity-modulated radiation therapy (IMRT) with the central shielding (CS) technique for patients with uterine cervical cancer. This retrospective study included 54 patients with International Federation of Gynecology and Obstetrics IB-IVA cancer. Whole pelvic radiotherapy or extended-field radiotherapy were performed at the dose of 50.4 Gy in 28 fractions with helical tomotherapy (HT). Six patients had para-aortic lymph node metastases. The CS technique with HT was utilized after a total dose of 28.8–41.4 Gy to reduce doses to the rectum and bladder. The prescribed dose of intracavitary brachytherapy was mainly 18–24 Gy in three or four fractions at point A. Concurrent chemotherapy was used for 47 patients (87%). Median follow-up time was 56 months. Seventeen patients (31%) developed recurrence. The recurrence of the cervix was observed in two patients (4%). The 5-year rates of the locoregional control, progression-free survival (PFS) and overall survival were 79, 66 and 82%, respectively. Among several factors evaluated, histological type of adenocarcinoma was only a significantly worse prognostic factor for PFS by multivariate analysis (hazard ratio, 4.9 [95% confidence interval, 1.3–18], P = 0.018). Grade 2 or higher late toxicities were observed in nine patients (17%). Two patients (4%) each had grade 3 proctitis and grade 3 ileus, respectively. No grade 4 toxicity or treatment-related death was observed. The results suggest that IMRT with the CS technique allows a high local control without increasing the risk of complications for cervical cancer patients.

Controversies in the Staging of Patients with Locally Advanced Cervical Cancer.

Approximately 10-25% of patients with locally advanced cervical cancer harbor metastases to the para-aortic lymph nodes. Staging of patients with locally advanced cervical cancer can be performed with imaging techniques, such as PET-CT; however, false negative rates can be as high as 20%, especially for patients with pelvic lymph node metastases. Surgical staging can identify patients with microscopic lymph nodes metastases and aid in accurate treatment planning with the administration of extended-field radiation therapy. Data from retrospective studies investigating the impact of para-aortic lymphadenectomy on the oncological outcomes of patients with locally advanced cervical cancer are mixed, while data from randomized controlled trials do not demonstrate a progression-free survival benefit. In the present review, we explore controversies in the staging of patients with locally advanced cervical cancer and summarize the available literature.

Prophylactic Extended-Field Irradiation Versus Pelvic Irradiation in Patients With Cervical Cancer With 2018 FIGO Stage IIIC1 Disease

To compare the survival rates and toxicities of prophylactic extended-field radiation therapy (EFRT) and pelvic radiation therapy (PRT) among cervical cancer patients with 2018 FIGO stage IIIC1 disease. We retrospectively analyzed patients with 2018 FIGO stage IIIC1 disease who were treated with definitive concurrent chemoradiotherapy at our institute between 2011 and 2015. A dose of 50.4 Gy in 28 fractions was delivered to the pelvic region (by PRT) or the pelvic plus para-aortic lymph node region (by EFRT) with intensity-modulated radiation therapy. The first-line regimen of concurrent chemotherapy was weekly cisplatin. A total of 280 patients were included, with 161 patients treated with PRT and 119 patients treated with EFRT. After propensity score matching (1:1), 71 pairs of patients were selected. The respective 5-year rates of the patients treated with PRT and EFRT were 61.9% and 85.0% for overall survival (p=0.025), 53.0% and 77.9% for disease-free survival (DFS, p=0.004) after matching. In the subgroup analysis, patients were grouped into a high-risk group (122 patients) and a low-risk group (158 patients) based on three factors: positive common iliac lymph nodes, ≥ 3 pelvic lymph nodes and 2014 FIGO stage IIIB disease. In both the high-risk and low-risk groups, EFRT significantly improved DFS compared with PRT. The rates of ≥ grade 3 chronic toxicities were 1.2% and 5.9% in the PRT and EFRT groups, respectively (p=0.067). In comparison to PRT, prophylactic EFRT was associated with improved OS, DFS, and PALN control in cervical cancer patients with FIGO stage IIIC1 disease. The incidence of grade 3 or higher toxicities was higher in the EFRT group than in the PRT group, although the difference was not significant.

Multicentric development and evaluation of 18F-FDG PET/CT and MRI radiomics models to predict para-aortic lymph node involvement in locally advanced cervical cancer.

To develop machine learning models to predict para-aortic lymph node (PALN) involvement in patients with locally advanced cervical cancer (LACC) before chemoradiotherapy (CRT) using 18F-FDG PET/CT and MRI radiomics combined with clinical parameters. We retrospectively collected 178 patients (60% for training and 40% for testing) in 2 centers and 61 patients corresponding to 2 further external testing cohorts with LACC between 2010 to 2022 and who had undergone pretreatment analog or digital 18F-FDG PET/CT, pelvic MRI and surgical PALN staging. Only primary tumor volumes were delineated. Radiomics features were extracted using the Radiomics toolbox®. The ComBat harmonization method was applied to reduce the batch effect between centers. Different prediction models were trained using a neural network approach with either clinical, radiomics or combined models. They were then evaluated on the testing and external validation sets and compared. In the training set (n = 102), the clinical model achieved a good prediction of the risk of PALN involvement with a C-statistic of 0.80 (95% CI 0.71, 0.87). However, it performed in the testing (n = 76) and external testing sets (n = 30 and n = 31) with C-statistics of only 0.57 to 0.67 (95% CI 0.36, 0.83). The ComBat-radiomic (GLDZM_HISDE_PET_FBN64 and Shape_maxDiameter2D3_PET_FBW0.25) and ComBat-combined (FIGO 2018 and same radiomics features) models achieved very high predictive ability in the training set and both models kept the same performance in the testing sets, with C-statistics from 0.88 to 0.96 (95% CI 0.76, 1.00) and 0.85 to 0.92 (95% CI 0.75, 0.99), respectively. Radiomic features extracted from pre-CRT analog and digital 18F-FDG PET/CT outperform clinical parameters in the decision to perform a para-aortic node staging or an extended field irradiation to PALN. Prospective validation of our models should now be carried out.

Isolated para-aortic nodal recurrence after treatment of early stage cervical carcinoma

ObjectiveSurgical evaluation of lymph node metastasis is paramount in the treatment of cervical cancer. We sought to explore the outcomes of patients with and without para-aortic lymphadenectomy undergoing curative-intent radical hysterectomy for stage IA-IIA cervical cancer. MethodsInstitutional data were retrospectively reviewed to identify women undergoing curative-intent radical hysterectomy with concurrent lymphadenectomy for stage IA-IIA cervical carcinoma from 2004 to 2021. Any carcinoma histology was allowed. Clinical risk stratification was performed according to GOG 92 and GOG 109 protocols. Disease outcomes, patterns of recurrence, and survival were analyzed with Chi square, t-test, Kaplan-Meier, and Cox proportional hazards multivariable statistics. Results300 patients were identified, 265 met inclusion criteria. Median follow up was 56 months. Pelvic lymphadenectomy (PLND) was performed in 71%, with the remainder undergoing combined para-aortic dissection (PPaLND). Baseline patient demographics and presence of clinical risk factors were well balanced between groups. PPaLND was more common in patients undergoing open surgery (OR 10.58, p <.0001), and tumors were larger in this group (2.96 vs 2.12 cm, p = .0002) and more likely non-squamous histology (OR 2.02, p = .017). Recurrence of disease was present in 13% of cases, with no difference between PLND and PPaLND regardless of histology. There were zero cases of isolated PaLN recurrence in either group. Neither progression free nor overall survival was different between groups. Prophylactic extended field radiation (EFRT) was not prescribed. ConclusionOmission of PaLN dissection, in the absence of suspicious nodes, did not decrease survival. There were no isolated PaLN recurrences after PLND alone.