Pelvic Intensity-modulated Radiotherapy Research Articles

Association of bowel radiation dose-volume with skeletal muscle loss during pelvic intensity-modulated radiotherapy in cervical cancer.

Radiation-induced bowel damage may compromise nutrient absorption and digestion and affect body composition during pelvic radiotherapy in patients with locally advanced cervical cancer (LACC). This study aimed to evaluate the relationship between bowel radiation dose-volume and body composition changes during pelvic radiotherapy. Data of 301 LACC patients treated with chemoradiotherapy were analyzed. Changes in skeletal muscle index (SMI) and density (SMD), and total adipose tissue index (TATI) were measured from computed tomography images at the L3 vertebral level. A reduction in SMI, SMD, or TATI of ≥10% was classified as "loss." Bowel V45 indicates the bowel volume (mL) receiving a radiation dose of ≥45 Gy. The relationship between body composition and bowel V45 was analyzed using logistic regression models. After treatment, 61 (20.3%), 81 (26.9%), and 97 (32.2%) patients experienced SMI, SMD, and TATI loss, respectively. Increased bowel V45 was independently associated with increased odds of SMI loss (odds ratio [OR]: 1.012; 95% confidence interval [CI]: 1.007-1.018; p<0.001) and TATI loss (OR: 1.006; 95% CI: 1.001-1.010; p=0.01), but not with SMD loss (OR: 1.005; 95% CI: 1.000-1.009; p=0.054). The cut-off value with the highest accuracy for predicting SMI loss was V45 ≥222 mL; a higher rate of SMI loss was noted in 40.0% of patients with V45 ≥222 mL than in 13.7% of patients with V45 <222 mL (p<0.001). Higher bowel dose-volume was significantly associated with muscle loss during pelvic radiotherapy. Bowel dose-volume consideration is required in individualized nutritional counseling and supportive care in clinical practice.

Influence of Pelvic Intensity-Modulated Radiation Therapy With Concurrent Cisplatin-Based Chemotherapy of Cervical Cancer on the Vaginal Microbiome.

Pelvic intensity-modulated radiation therapy (IMRT) combined with concurrent chemotherapy is an effective treatment for cervical cancer; however, radiation resistance impairs its clinical benefit. The vaginal microbiome plays an important but poorly understood role in cancer radiochemotherapy. In this study, we investigated the effects of treatment on the overall composition and alteration of the vaginal microbiome in patients receiving pelvic IMRT with concurrent cisplatin-based chemotherapy. We collected samples from twenty patients with cervical cancer and six healthy controls and performed 16S rRNA sequencing. Vaginal microbial composition analysis revealed significant differences between the two groups, but no significant differences between radiation treatment time points. However, the relative abundances of Gammaproteobacteria, Gemmatimonadetes, Gemmatimonadales, Pseudomonadales, Gemmatimonadaceae, Rikenellaceae, Acinetobacter, Desulfovibrio, Prevotella 9, Rikenellaceae RC9 gut group, Turicibacter, and the metagenome increased with time. The results encourage further study into the effects of the vaginal microbiome on cervical cancer treatment strategies, especially radiochemotherapy. Better understanding of these effects could inform new therapeutic approaches to enhance the efficacy of radiochemotherapy.

Intensity-modulated radiotherapy combined with intracavitary brachytherapy for locally advanced cervical cancer with uterus didelphys

The purpose of this study was to investigate the clinical application of intensity-modulated radiotherapy combined with intracavitary radiotherapy for locally advanced cervical cancer complicated with uterus didelphys. We retrospectively reviewed the medical records of six patients with locally advanced cervical cancer associated with uterine malformations treated at the National Cancer Center/Cancer Hospital (Beijing, China) between 2015 and 2018. Six cases, including cervical squamous cell carcinoma (n = 3), cervical adenocarcinoma (n = 2), and clear cell adenocarcinoma (n = 1) were identified by pathological diagnosis. Uterine malformation included uterus didelphys (n = 6), with vaginal subseptum (n = 2). Six cases were treated with pelvic intensity-modulated radiotherapy. Four patients received three- dimensional intracavitary brachytherapy based on computed tomography, and two patients received conventional two-dimensional intracavitary brachytherapy. The acute and delayed responses of gastrointestinal and genitourinary toxicities were ≤grade 2 in 5 patients. Five patients achieved clinical complete remission and four patients had no recurrence during the follow-up period. One patient with cervical adenocarcinoma expired due to progression of the disease. The clinical results suggest that advanced cervical cancer associated with uterus didelphys required individual radiotherapy. The use of intensity-modulated radiotherapy combined with three-dimensional intracavitary brachytherapy is recommended in concurrent chemoradiotherapy.

Efficacy and safety of berberine in the prophylactic treatment of acute radiation proctitis in postoperative patients with cervical cancer: a randomized controlled study*

Abstract Objective The aiom of this study was to study the efficacy and safety of berberine as a prophylactic treatment of acute radiation proctitis in postoperative patients with cervical cancer. Methods A total of 120 postoperative patients with cervical cancer were enrolled between July 2016 and October 2019, and randomly divided into a treatment group (berberine 300 mg three times a day, n = 60) and a control group (receiving vitamin C tablets, 100 mg three times a day; n = 60) using the random number table method. All patients received pelvic intensity-modulated radiation therapy (IMRT) and concurrent sensitizing chemotherapy weekly. The difference in the percentage of irradiation volume to the rectum and small intestine as well as the incidence, onset time, severity, and duration of acute radiation proctitis and cystitis during radiotherapy were compared between the two groups. The completion rate, completion time, number of chemotherapy sessions, and quality of life during radiotherapy were also compared. Results There were no statistical differences in age, FIGO stage, pathological type, complications, high-risk factors, and rectum and small intestine irradiation dose distribution (V20, V30, V40, and V50) between the two groups (P &gt; 0.05). No acute radiation proctitis of grade 3 or above occurred in the two groups. There was no significant difference in the incidence of acute radiation cystitis, grade 2 acute radiation proctitis, completion rate of IMRT, and frequency of sensitization chemotherapy between the two groups. After prophylactic treatment with berberine, the incidence of grade 1 acute radiation proctitis, occurrence of grade 1 radiation proctitis, and completion time of radiotherapy in the treatment group were significantly lower than those in the control group (P &lt; 0.05). The SF-36 score of the treatment group after radiotherapy was 67.53 ± 4.21, which was significantly better than that of the control group (64.90 ± 6.32; P &lt; 0.05). The incidence of grade 3-4 neutropenia in the treatment group was 10% and lower than that in the control group (31.7%, P = 0.003). No adverse reactions related to berberine were observed. Conclusion Prophylactic prescription with oral berberine can reduce the incidence, onset time, and duration of grade 1 acute radiation proctitis, and improve the quality of life of postoperative patients with cervical cancer receiving concurrent chemoradiotherapy.

Extended field or pelvic intensity-modulated radiotherapy with concurrent cisplatin chemotherapy for the treatment of post-surgery multiple pelvic lymph node metastases in cervical cancer patients: a randomized, multi-center phase II clinical trial.

BackgroundTo prospectively compare the outcomes and side effects between groups of postoperative cervical cancer patients with multiple pelvic lymph node metastases who were treated with extended field or pelvic intensity-modulated radiotherapy (IMRT) with concurrent cisplatin chemotherapy.MethodsCervical carcinoma patients with International Federation of Gynecology and Obstetrics (FIGO) stage Ib-IIa, who underwent radical hysterectomy and had histologically confirmed multiple (≥2) pelvic lymph node metastases, were enrolled into this study. The patients were randomly assigned to pelvic-IMRT or extended field-IMRT (45 Gy/25 Fx) group. Patients in either group received concurrent cisplatin chemotherapy (40 mg/m2) starting on the first day of irradiation.ResultsUntil December 31th 2017, 129 patients were initially enrolled into this study. During the study, 3 patients were dropped out due to either incompletion of the study or exclusion by the criteria. Consequently, 64 patients completed pelvic-IMRT, and 62 patients completed extended field-IMRT. Median follow-up period was 61.30 months in the extended field-IMRT group and 60.60 months in the pelvic-IMRT group. Five-year actuarial survival probability was 0.759 (95% CI: 0.619–0.854) in the extended field-IMRT group which was not significantly different from that of the pelvic-IMRT group [0.824 (95% CI: 0.690–0.905), P=0.442]. Similarly, the five-year progression-free probability was 0.720 (95% CI: 0.576–0.822) in the extended field-IMRT group, which was not significantly different from that of the pelvic-IMRT group [0.781 (95% CI: 0.637–0.874), P=0.389]. In addition, there was no significant difference between the two groups in hematology and gastrointestinal tract toxicities.ConclusionsPost-operative pelvic-IMRT or extended field-IMRT with concurrent cisplatin chemotherapy had similar outcomes in terms of survival rates and adverse events in cervical carcinoma patients at FIGO stage Ib-IIa with multiple pelvic lymph nodes metastases.

Long-Term Results of Concurrent Chemoradiotherapy Combined with Anti-EGFR Monoclonal Antibody Prior to Surgery in Locally Advanced Cervical Cancer: A Single-Institute Prospective Study.

PurposeWe aimed to evaluate the long-term survival outcomes of concurrent chemoradiotherapy (CCRT) combined with nimotuzumab followed by surgery in patients with locally advanced cervical cancer (LACC).Patients and MethodsPatients received whole pelvic intensity-modulated radiation therapy (IMRT) and concomitantly with weekly cisplatin (40 mg/m2) or nedaplatin (30 mg/m2) and weekly nimotuzumab (200 mg). After assessment of the treatment response, patients then underwent radical surgery.ResultsBetween June 2013 and July 2016, 33 patients with FIGO IB2–IIIB cervical cancer were recruited. Clinical complete response and partial response were observed in 8 (24.3%) and 23 patients (69.7%), respectively. Twenty-seven patients (81.8%) were successfully treated with radical hysterectomy and pelvic lymphadenectomy: 9 (33.3%) showed pathological complete response; 10 (37.1%) showed partial response and 8 (29.6%) presented with persistent macroscopic/microscopic residual carcinoma. For the intention-to-treat population, the median follow-up time was 53.7 months. Locoregional recurrence and distant metastases were observed in three and seven patients, respectively. The 5-year overall survival, progression-free survival, locoregional recurrence-free survival, and distant metastasis-free survival were 81.5%, 72.7%, 90.9%, and 78.3%, respectively. Both acute and late toxicities were manageable and mainly limited to grade 1 or 2.ConclusionConcurrent chemoradiotherapy combined with nimotuzumab followed by surgery for patients with LACC is safe and results in excellent long-term treatment outcomes. Further randomized controlled studies are warranted to confirm the findings.

PH-0232: Metabolic profiles do not recover to normal after pelvic IMRT for high-risk prostate cancer.

PH-0232: Metabolic profiles do not recover to normal after pelvic IMRT for high-risk prostate cancer.

Clinical Results Of Proton Boost Combined With Pelvic IMRT For Node-Positive Prostate Cancer: Dosimetric Analysis And Patient-Reported Outcomes

Previous studies demonstrated the efficacy of radiation therapy for clinically node-positive prostate cancer. However, there are few reports on treatment strategies incorporating proton therapy. The purpose of this study was to evaluate the clinical outcome of pelvic IMRT combined with proton boost for node-positive prostate cancer, including toxicity and patient reported outcomes (PROs) of health-related quality of life (QOL), and to perform dosimetric comparison of boost plans between proton therapy and IMRT. From March 2013 to May 2016, 12 patients with node-positive prostate adenocarcinoma were treated by pelvic IMRT with 45 Gy/25 fr followed by proton boost with 34 GyE/17 fr to the prostate and seminal vesicles and 26 GyE/13 fr to positive lymph nodes. Biochemical failure was defined according to the Phoenix definition. Adverse effects were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Dosimetric comparisons were carried out between proton therapy and IMRT regarding boost plans. The same CTVs, dose fractionation and target volume coverage, and OAR dose constraints were used. All 12 patients completed the Expanded Prostate Cancer Index Composite (EPIC) health-related QOL questionnaire before and at 1-36 months after treatment. The median follow-up period was 59 months (range, 42-80 months). The Gleason score was 7 in 1 patient, 8 in 3 patients, and 9 in 8 patients. The median PSA level before treatment was 38.8 ng/ml (range, 11-230). All patients underwent androgen deprivation therapy for a median duration of 48.5 months. Three patients had biochemical failure. Two of them experienced extrapelvic recurrence. There was no grade 3 or higher acute or late GI and GU toxicity. Planning target volume coverage by the prescription dose was similar between the proton and IMRT plans. In the proton plan, mean rectum V40Gy was significantly lower than in the IMRT plan (44.4% vs 59.3%). The dose to the small intestine for 1 cc and to the colon for 1 cc was 45.1 and 52.3 Gy, respectively, in the proton plans, and 47.0 and 55.7 Gy, respectively, in the IMRT plans, but there were no significant differences. Mean bowel bother score and bowel function score at 6-36 months were similar to or greater than the scores before treatment. Mean urinary summary QOL score was 86.2 before treatment and 82.0, 92.0, 86.7, and 89.8 at 1, 6, 12, and 36 months, respectively. Proton boost combined with pelvic IMRT was feasible and offered reductions in radiation doses to gastrointestinal organs at risk in patients with node-positive prostate cancer. No grade 3 AEs were observed after IMRT plus proton boost and no change was noted in PROS scores. Further studies are warranted for a larger population.

Impact of Pelvic Intensity-modulated Radiotherapy (IMRT) on Lymph Node Coverage and Dose to Critical Organs, Compare to Three-Dimensional Conformal Radiation Therapy (3D-CRT), in Localized High-Risk Prostate Cancer

Men with high risk prostate cancer (HR-PrCa) are typically treated with combined androgen deprivation therapy and curative radiotherapy (RT) consisting of pelvic nodal and prostate/seminal vesicle (PrSV) irradiation followed by PrSV boost RT. 3D-CRT or IMRT are used for the treatment of pelvic nodes. A phase II randomized study examining the effect of RT technique on patient Quality of Life (QoL) was completed in our institution. Here, we report an early analysis of the dosimetric impact of 3D-CRT versus IMRT in patients participating in this study. A total of 105 men with HR-PrCa were randomized at 1:1 ratio to receive either pelvic 3D-CRT (standard 4-field conformal technique) or multi-beam IMRT, consisting of 4500cGy in 25 fractions to planning target volume (PTV) 1, followed by boost RT to PTV2 of 2496cGy in 13 fractions. The latter was delivered using a 7-field IMRT in all patients. Organs at risk (OAR) and clinical target volumes (CTV) were delineated on CT simulation images. The lymph node target included the common, internal, external iliac, obturator and pre-sacral lymph nodes in accordance with RTOG guidelines. CTV1 consisted of nodal CTV plus PrSV. CTV2 was minimized to PrSV. The PTV consisted of an expansion of 7 mm beyond CTV. For consistency, in comparison between the two techniques, IMRT fields were modified to results to similar superior border coverage as 3D-CRT, at the level of L5-S1. Bladder and rectum were contoured as solid organs. To take inter-fractional bowel motion into account, bowel was delineated as whole pelvic and abdominal cavity excluding bones, muscle, and other OAR. Pelvic RT with 3DCRT missed significant percentage of pelvic nodal volume. PTV1 D95% showed mean difference of -4.96, 95% CI (-6.41, -1.74); p = 0.0013 and D99% showed mean difference of -11.56, 95% CI (-14.96, -8.17); p< 0.00001 in favor of IMRT. There was significant difference in PTV1 heterogeneity index (D2%-D95%/D50%) (Mean diff = 0.22, 95%CI (0.14, 0.29); P<0.00001). IMRT decreased dose to OAR. Rectum V30 was 97% in 3DCRT compare to 93.41% in IMRT arm with absolute difference of 3.81% (95% CI (1.52, 6.11); P = 0.0014). Bladder V40 and V50 were significantly reduced (V40: 84 % vs 62% for 3DCRT vs IMRT, absolute difference of 22% (95%, CI (15.55, 28.2); P<0.0001); V50 absolute reduction of 18% with IMRT (95%, CI (11.53, 24.48); P<0.0001). Similarly, IMRT reduced total body/bone irradiation significantly. This randomized study of 3D-CRT versus pelvic IMRT is an appropriate setting to investigate the dosimetric impact of pelvic IMRT and help define its potential benefits on patient QoL. This early analysis suggests that utilization of IMRT for pelvic RT could offer dosimetric advantages by improve lymph node coverage and reducing RT dose to OAR. The results are in agreement with an improved bowel-related QoL observed in this study. On-going analysis examines correlations between dosimetric and patient QoL data.

Definitive Intent Locoregional IMRT In Oligometastatic Anal Squamous Cell Carcinoma

The role of locoregional intensity modulated radiation therapy (IMRT) in patients with metastatic anal squamous cell carcinoma (SCC) remains undefined. There is growing evidence of the potential benefit of local therapy even in the setting of oligometastatic disease to prevent the morbidity of uncontrolled pelvic disease. We queried an institutional database of 358 consecutive patients with SCC of the anal canal treated with definitive intent pelvic IMRT from 2005 to 2018 to identify patients with de novo metastatic disease. Locoregional control (LRC), progression-free survival (PFS), and overall survival (OS) were computed using the Kaplan-Meier method. Acute and late toxicities were assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Twenty-five patients with a median follow-up of 26 months including 19 (76%) women and 6 (24%) men with a median age of 60 years comprised the evaluable cohort. Eight (32%) patients had a solitary metastasis, 10 (40%) had two metastatic lesions, 2 (8%) had three metastatic lesions, 5 (20%) had four or more metastatic lesions. Non-regional lymph nodes were the most common site of metastatic disease (N = 16, 49%) followed by liver (N = 10, 30%), lung (N = 4, 12%), and others (N = 3, 9%). Sixteen patients had HPV related disease and 3 patients were HIV+. The median dose to the primary tumor was 56Gy (range, 50-58Gy) in a median of 28 fractions (range, 25-29) over a median of 39 elapsed days (range, 35-55). Twelve (48%) patients received induction chemotherapy and all patients received concurrent chemotherapy predominately mitomycin and capecitabine based. Twenty-one (84%) patients had metastatic-directed ablative therapy which included radiation (N = 20, 80%) and IR-ablation (N = 1, 4%). No patients underwent metastasectomy or received additional chemotherapy, targeted therapy, or immunotherapy prior to progression of disease. The 3-year LRC was 81%, PFS was 27%, and OS was 53%. In comparing patients with non-regional lymph node involvement to patients with visceral organ involvement there was no significant difference in LRC (86% vs. 79%, p = 0.950) but a trend for improved PFS (71% vs. 18%, p = 0.069) and OS (86% vs. 49%, p = 0.365). Grade 3+ acute toxicity included dermatitis (12%), proctitis (4%), and diarrhea (4%). Late grade 2+ toxicity rate was 12%. Definitive intent pelvic IMRT provides excellent locoregional control in patients with oligometastatic anal SCC. Local and extended regional nodal radiation is important to prevent the significant morbidity of uncontrollable pelvic disease given durable PFS and OS in patients with oligometastatic anal SCC.

Long-term outcomes of intensity-modulated radiation therapy (IMRT) and high dose rate brachytherapy as adjuvant therapy after radical hysterectomy for cervical cancer

ObjectiveCompared with 3D-planned pelvic radiation, intensity-modulated radiation therapy (IMRT) has been shown to reduce acute toxicity in cervical cancer patients after radical hysterectomy. This study evaluated late toxicity and patterns...

Results of the ADRRAD Trial of pelvic IMRT plus radium-223 in men with mHSPC metastatic to bone.

136 Background: Radiotherapy to the Prostate in mHSPC improves overall survival (OS) and Progression free survival (PFS) for patients with low-volume-disease[1]. Radium-223 in metastatic castration resistant prostate cancer (mCRPC) improves OS [2]. We conducted a prospective phase 1/2 clinical trial in mHSPC, testing the combination of with LHRHa, concurrent pelvic radiotherapy and radium-223. Methods: Thirty patients were recruited with mHSPC; they had a minimum of 3 bone metastases (majority had &gt; 20 bone mets), nil visceral metastases, PS0-1. Patients were encouraged to receive up front docetaxel. They were treated with ongoing LHRHa, pelvic radiotherapy aiming for 74Gy in 37 fractions to prostate PTV with 60Gy concomitantly delivered to pelvic nodal PTV. Concurrently, patients received radium-223, 55kBq/kg for 6 cycles q28 days; fraction 1 radiotherapy was synchronous with cycle 1 day 1 radium-223. Results: Median age was 63 years and 28 (93%) received at least 4 cycles of docetaxel. One patient received prostate only radiotherapy due to bowel constraints. Three patients had cycle 6 radium-223 omitted. At a median follow-up of 28 months, there have been 415 Adverse events, (3% Grade &gt;3), and 6 serious adverse events (SAEs) ( 2 episodes of UTI, 1 each of cystitis non-infective, cardiac chest pain, pyrexia and AKI). Commonest AEs by number were: leucopenia, neutropenia, and diarrhoea. Ten SSE’s have occurred including 8 courses of palliative radiotherapy for bone pain, 1 course of radiotherapy for impending MSCC and 1 pathological fracture. At median follow up 28.0 months, median biochemical PFS is 17.9 months, median OS not yet reached. Conclusions: This trial shows clear tolerability and promising early efficacy data requiring further exploration in a randomised phase 3 trial. Clinical trial information: 2014-000273-39.

Long-course neoadjuvant chemoradiotherapy with versus without a concomitant boost in locally advanced rectal cancer: a randomized, multicenter, phase II trial (FDRT-002)

BackgroundThis study was designed to explore whether an intensified chemoradiotherapy (CRT) led to a better clinical outcome in locally advanced rectal cancer.MethodsPatients with stage II/III rectal cancer were randomly allocated to receive either pelvic intensity-modulated radiation therapy (IMRT) of 50 Gy/25Fx concurrently with capecitabine and oxaliplatin (Arm A), or pelvic radiation of 50 Gy/25Fx with a concomitant boost of 5 Gy to the primary lesion, followed by a cycle of XELOX 2 weeks after the end of CRT (Arm B). All patients were planned to receive a definitive operation 8 weeks after the completion of CRT and a total of six perioperative chemotherapy cycles of capecitabine and oxaliplatin regardless of pathological result. Pathological complete response (ypCR) was the primary endpoint.ResultsFrom February 2010 to December 2011, 120 patients from three centers were enrolled in this study. Ninety-five percent patients completed a full-dose chemoradiotherapy as planning. Then 53 and 57 patients received a radical surgery, and 8 and 14 cases were confirmed as ypCR in two groups (P = 0.157). The other 10 patients failed to receive a definitive resection because of unresectable disease. Similar toxicities were observed between two groups and more incision healing delay were found in Arm B (3 vs.13, P = 0.011). No statistical differences were observed in local-regional control (P = 0.856), disease-free survival (P = 0.349) and overall survival (P = 0.553). Mesorectal fascia (MRF) involvement was an independent prognostic factor for survival in multivariate analysis.ConclusionsA concomitant boost to oxalipatin-combined preoperative chemoradiotherapy demonstrated a slightly higher pCR rate but delayed incision healing after surgery. The impact of MRF involvement on survival merits further investigations.Trial registrationNCT01064999 (ClinicalTrials.gov).

Risk of Pelvic Fracture With Radiation Therapy in Older Patients

Older patients undergoing radiation therapy (RT) for pelvic malignancies are at increased risk for pelvic fracture, which is associated with significant morbidity and mortality. RT techniques such as brachytherapy or intensity modulated RT (IMRT) allow for more conformal dose distributions, but it is not known whether the risk for pelvic fracture varies by RT modality. This observational cohort study involved 28,354 patients ≥65 years old, treated with RT for pelvic malignancies. We evaluated the relative risk of pelvic fracture by type of RT when accounting for baseline factors. To test for nonspecific effects, we also evaluated risk of nonpelvic fractures in the same population. The 5-year incidence of pelvic fractures was 12.7% (95% confidence interval [CI], 11.6%-13.8%), 11.8% (10.8%-12.8%), and 3.7% (3.4%-4.0%) for patients with gastrointestinal, gynecologic, and prostate cancer, respectively. On multivariable analysis, being treated with IMRT (hazard ratio, 0.85; 95% CI, 0.73-0.99) or brachytherapy therapy alone (hazard ratio, 0.43; 95% CI, 0.34-0.54) was associated with a reduced hazard for pelvic fractures compared with 3D conformal radiation therapy in female patients. In contrast, there was no association with RT modality and the hazard for nonpelvic fractures among females. There was no significant association between pelvic fractures and IMRT or brachytherapy for male patients. White race, advanced age, and higher comorbidity were associated with an increased hazard for pelvic fracture. IMRT and brachytherapy were associated with a reduced risk of pelvic fractures in older women undergoing RT for pelvic malignancies. Pelvic insufficiency fracture risk should be considered when treating with pelvic RT.

158 Impact of Pelvic Intensity-Modulated Radiotherapy (IMRT) on Lymph Node Coverage and Dose to Critical Organs, Compare to Three-Dimensional Conformal Radiation Therapy (3D-CRT), in Localized High-Risk Prostate Cancer

158 Impact of Pelvic Intensity-Modulated Radiotherapy (IMRT) on Lymph Node Coverage and Dose to Critical Organs, Compare to Three-Dimensional Conformal Radiation Therapy (3D-CRT), in Localized High-Risk Prostate Cancer

Adjuvant Bone-Marrow Sparing IMRT in Endometrial Cancer Patients Treated with Sequential Chemotherapy- Does it Help with Completion Rate?

Postoperative pelvic IMRT has been shown to have decreased rates of myelosuppression in patients with gynecologic cancers treated with concurrent chemoradiation therapy, when compared to conventional 3D-CRT. However, there is limited data on how marrow sparing IMRT might impact tolerance in the setting of full-dose sequential chemotherapy and extended-field radiotherapy. A retrospective analysis of 158 patients with endometrial cancer treated with adjuvant sequential chemoradiation therapy with marrow sparing IMRT from 2008-2018 was performed. 146 of 158 patients received pre-IMRT chemotherapy, with 14 of 158 receiving post-IMRT chemotherapy. 63 patients were treated with extended field IMRT to include para-aortic lymph nodes, while 95 were treated with pelvic field IMRT including the entire common iliac region. Bone marrow was defined dosimetrically as the pelvic bone, bilateral femoral heads, and lower lumbosacral spine, with goal bone marrow V20 Gy < 80%. Myelosuppressive events were categorized using RTOG criteria. Linear regression analysis was used to assess for correlation between myelosuppression events and bone marrow dose. 157 of 158 (99.4%) patients completed EBRT as prescribed, with 1 discontinuing treatment due to acute GI toxicity. Median EBRT treatment time was 35 days (range 32-60 days). Total EBRT treatment time was 40 days or more in 17 patients (11%), with 4 patients having prolonged EBRT treatment time attributable to myelosuppression (range 42-57 days). All 158 patients had CBCs during treatment (median 4, range 1-8). Results for myelosuppressive events are detailed in the table below. Bone marrow V20 <80% was met in 118/158 (75%) of patients. Median bone marrow mean dose was 29.1 Gy (range 19.4-35.8 Gy). Median bone marrow V20 Gy was 73.9% (range 47.1-91.0%). Linear regression analysis did not reveal statistically significant associations between V20 Gy or mean bone marrow dose with grade 2 myelosuppression events. Grade 3 myelosuppression were rare events, with 2% incidence in pelvic field IMRT and 5% incidence in extended field IMRT. This is the largest series with marrow sparing IMRT in patients with endometrial cancer treated with sequential chemoradiation therapy, showing very low rates of grade III myelosuppression and 99.4% completion rate, with few treatment interruptions. With our goal bone marrow V20 Gy <80% dose met in the majority of patients, we were unable to determine a statistically significant relationship between myelosuppression events and V20 Gy or mean bone marrow dose.Abstract 2808; Table 1Grade 2 Anemia (Hgb<9.5-7.5)Grade 3 Anemia (Hgb <7.5)Grade 2 Neutropenia (ANC <1500-1000)Grade 3 Neutropenia (ANC <1000)Grade 2 Thrombocytopenia (PLT<75-50)Grade 3 Thrombocytopenia (PLT<50)Any Myelosuppression EventAny Grade 3 EventFrequency (n=158)20/158 (13%)0/158 (0%)33/158 (21%)4/158 (3%)8/158 (5%)1/158 (1%)53/158 (34%)5/158 (3%) Open table in a new tab

Intensity-Modulated Versus Three-Dimensional Conformal Radiotherapy for Cervical Cancer: National Trend and Survival

Definitive chemo-radiotherapy is the standard of care for locally advanced cervical cancer. Recently, a randomized trial showed pelvic intensity-modulated radiotherapy (IMRT) was associated with significantly less GI and urinary toxicities than three-dimensional radiotherapy (3DRT). The purpose of this study is to determine the trend of IMRT use in the United States and to determine if IMRT is associated with better survival compared to 3DRT. The National Cancer Database (2004-2015) was analyzed to evaluate the practice pattern and overall survival (OS) for localized cervical cancer patients treated with chemotherapy with pelvic IMRT or 3DRT. Those without treatment, treated by chemotherapy alone, RT alone or surgery, were excluded. OS was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards models, and propensity score-matched analyses. IMRT use increased from 32.6% to 68.1% in the United States. IMRT use was associated with later years of diagnosis, academic facility, nodal positive disease, and no brachytherapy use. At a median follow-up of 31.0 months, there was no survival difference between IMRT versus 3DRT by both univariate (HR, 0.97; P=0.57) and multivariate analysis (HR, 0.95; P=0.33). Propensity score analysis with matched baseline characteristics including brachytherapy use re-demonstrated a similar survival between IMRT and 3DRT with median survival (82.5 vs 77.0 months), 2-year OS (72.9% vs 72.4%) and 5-year OS (55.3% vs 54.9%) (HR, 0.95; P=0.41). IMRT has become the major treatment modality in the United States, preferred to 3DRT for locally advanced cervical cancer. However, there is no survival difference between IMRT and 3DRT.

Rectal Motion During Intensity Modulated Radiotherapy for Post-Hysterectomy Endometrial and Cervical Cancer Patients

Intensity modulated radiotherapy (IMRT) is often used in gynecologic cancer in the post-operative setting with defined volume guidelines. It delivers a highly conformal treatment, reducing normal tissue irradiation, but results in a sharp dose gradient at the treatment volume edge. Significant vaginal cuff motion can occur due to intra- and inter-fraction motion of the rectum and bladder, which may cause inadequate target coverage. There is no consensus on how to account for the effects of rectal filling on this motion. We sought to quantify inter-fraction rectal motion during the full course of IMRT treatment and to describe if rectal motion varied by week of treatment delivery or by level within the pelvis. We retrospectively reviewed thirty consecutive patients with endometrial or cervical cancer status post hysterectomy who received IMRT to the vaginal cuff and regional lymphatics. Two reviewers measured differences in rectal position between the initial planning CT and cone-beam CT (CBCT) scans obtained daily. Department policy recommended patients be treated with full bladder daily and those with significant rectal filling asked to empty their bowels. Differences were obtained for scans obtained the first day of each week of treatment and on the final treatment date for the five weeks. At each time point, reviewers quantified anterior rectal wall movement in the anterior-posterior axis at six pre-determined levels from S4-S5 superiorly to 4 cm below the inferior border of S5 inferiorly. The resulting measurements were reviewed, and any discrepancies > 2 mm were resolved by a tertiary review. The average displacement for all patients at all timepoints and pelvic landmarks was 0.36 cm posteriorly. The maximum anterior and posterior displacements of the sample population were 3.78 cm and 4.73 cm, respectively. The average displacement did not meaningfully vary by week, measuring 0.31 cm, 0.47 cm, 0.39 cm, 0.32 cm, and 0.33 cm, all posteriorly. However, greater displacement was noticed higher in the pelvis. From superior to inferior, average displacements were 0.47 cm, 0.43 cm, 0.48 cm, 0.35 cm, 0.32 cm, and 0.18 cm, all posteriorly. 95% of all displacements fell between 2.55 cm posteriorly and 1.82 cm anteriorly. No previous studies have examined rectal displacement in the anterior-posterior axis over the course of treatment and at different levels within the pelvis for cervical and endometrial cancers. Our findings indicate significant displacement exists and that pelvic IMRT planning may benefit from anterior and posterior margins above those recommended by current guidelines. At a minimum, the results support the need for daily CBCT imaging to assess rectal filling and to develop institution guidelines for managing large displacements. In addition, margin recommendations may differ based on the level within the pelvis.

Postoperative pelvic intensity-modulated radiation therapy reduced the incidence of late gastrointestinal complications for uterine cervical cancer patients.

The aim of the study was to compare incidences of late gastrointestinal adverse events and clinical outcomes between 3D conformal radiation therapy (3DCRT) and intensity-modulated radiation therapy (IMRT) after radical hysterectomy for cervical cancer patients. Between March 2007 and May 2014, 73 cervical cancer patients with high-risk prognostic factors (pelvic lymph node metastasis and/or parametrial invasion) underwent postoperative pelvic radiation therapy (RT) after radical hysterectomy. Of these patients, 33 (45%) and 40 (55%) received 3DCRT and IMRT, respectively. Because the gastrointestinal obstruction rate after postoperative pelvic 3DCRT was high, no concurrent chemotherapy was applied until 2015. The median follow-up period for patients with 3DCRT and IMRT was 82 months (6–113) and 50 months (5–74), respectively. There was no significant difference in overall survival (OS) (4-year OS: 85% vs 78%, P = 0.744) or disease-free survival (DFS) (4-year DFS: 73% vs 64%, P = 0.696) between the two groups. Eleven (33%) and 13 (33%) patients experienced recurrence after 3DCRT and IMRT, respectively. The patients who had vaginal invasion from the postoperative pathological finding more frequently had loco-regional recurrence than the patients who did not have vaginal invasion (2.3% vs 17%, P = 0.033). Gastrointestinal obstruction was observed in 9 (27%) and 3 (7.5%) patients for 3DCRT and for IMRT, respectively (P = 0.026). Severe gastrointestinal obstruction that required surgery was observed in 6 (19%) patients, all of whom received adjuvant RT by 3DCRT. IMRT could reduce the incidence of late severe gastrointestinal obstruction after postoperative pelvic RT with a non-inferior clinical efficacy compared with 3DCRT.

Long-Term Survival and Late Toxicity Associated With Pelvic Intensity Modulated Radiation Therapy (IMRT) for Cervical Cancer Involving CT-Based Positive Lymph Nodes.

The purpose of this study was to evaluate the outcomes and toxicity experienced by cervical cancer patients with positive lymph nodes (LNs) who were treated with intensity-modulated radiation therapy (IMRT) and intracavitary brachytherapy (ICBT) plus concurrent chemotherapy. We retrospectively evaluated 108 cervical cancer patients with computed tomography (CT)-based positive LNs treated with IMRT and ICBT plus concurrent chemotherapy between 2009 and 2011. IMRT plans were designed to deliver 50 Gy to 95% of the planning target volume (PTV; cervical tumor, pelvis, and parametrium), with daily doses of 1.6–1.8 and 60–70 Gy to 95% of the planning gross tumor volume (PGTV)-LN (pelvic or para-aortic LNs), with daily doses of 2.0–2.2 Gy. Overall survival (OS) and progression-free survival (PFS) Kaplan–Meier curves were plotted. Acute and late toxicities were evaluated according to the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer toxicity criteria. Of the 108 cases, 45 were stage IIB and 63 were stage IIIB. The median follow-up was 65 months (range 2–83). Overall, the 5 year cumulative incidences of pelvic failure alone, distant failure alone, and synchronous pelvic and distant failure were 8.3, 12.9, and 8.3%, respectively. The 5 year OS rate was 67.6%, and the 5 year PFS rate was 53.7%. The 5 year cumulative incidence was 9.2% for late gastrointestinal and genitourinary toxicities of Grade ≥3 and 51.8% for acute leukopenia of Grade ≥3. The clinical results suggest that IMRT and ICBT with concurrent chemotherapy is an effective treatment, with acceptable toxicity, for advanced cervical cancer involving positive LNs.