Preoperative Intensity Modulated Radiation Therapy Research Articles

Concurrent preoperative eribulin and radiation for resectable retroperitoneal liposarcoma: a phase 1B study.

Management of retroperitoneal liposarcoma (RPLPS) is challenging and recurrence rates remain high despite aggressive surgical resections. Preoperative radiation alone lacks definitive benefit, thus we sought to evaluate combined chemoradiotherapy with the potential to enhance local efficacy of radiation as well as control micrometastatic disease. We assessed the safety and tolerability of preoperative eribulin, a cytotoxic microtubule inhibitor approved for the treatment of advanced liposarcoma, in combination with radiation in patients with RPLPS. In this open-label dose-finding study, patients with primary or recurrent resectable RPLPS received preoperative intensity-modulated radiation therapy (IMRT) with escalating doses of eribulin. Eribulin was administered for three 21-day cycles at a starting dose of 1.1 mg/m2. Concurrent radiation to 50.4 Gy began during cycle 1. Surgical resection occurred 3-10 weeks after completion of chemoradiation. The primary endpoint was determination of the recommended phase 2 doses (RP2D) of concurrent eribulin and radiation. Between 2018-2023, fifteen patients were enrolled. Thirteen patients were evaluable for dose-determination. Four patients treated at starting dose level had no dose-limiting toxicities (DLTs). Two of nine patients treated with escalated eribulin dose had DLTs. The RP2D was established as eribulin 1.4 mg/m2 and IMRT 50.4 Gy. Eleven patients were evaluable for secondary efficacy endpoints. The median recurrence-free survival was 30.4 months (95% CI 12.0-NR) and the median overall survival was 54.1 months (95% CI 9.5-NR). Patient reported outcome data did not show any significant changes over the study period. A preoperative chemoradiation protocol of eribulin in combination with IMRT showed a manageable safety profile and warrants additional prospective evaluation for treatment of resectable RPLPS.

1730P Preliminary results of phase II study on preoperative intensity-modulated radiotherapy with concurrent PARP inhibitor for patients with non-metastatic inoperable or borderline operable extremity and trunk soft tissue sarcoma

1730P Preliminary results of phase II study on preoperative intensity-modulated radiotherapy with concurrent PARP inhibitor for patients with non-metastatic inoperable or borderline operable extremity and trunk soft tissue sarcoma

Retracted: Hyperfractionation versus Conventional Fractionation of Preoperative Intensity-Modulated Radiotherapy with Oral Capecitabine in Locally Advanced Mid-Low Rectal Cancer: A Propensity Score Matching Study.

[This retracts the article DOI: 10.1155/2022/9119245.].

The Association of Rural Residence With Surgery and Adjuvant Radiation in Medicare Beneficiaries With Rectal Cancer

Radiation therapy and surgery are fundamental site-directed therapies for nonmetastatic rectal cancer. To understand the relationship between rurality and access to specialized care, we characterized the association of rural patient residence with receipt of surgery and radiation therapy among Medicare beneficiaries with rectal cancer. We identified fee-for-service Medicare beneficiaries aged 65 years or older diagnosed with nonmetastatic rectal cancer from 2016 to 2018. Beneficiary place of residence was assigned to one of 3 geographic categories (metropolitan, micropolitan, or small town/rural) based on census tract and corresponding rural urban commuting area codes. Multivariable regression models were used to determine associations between levels of rurality and receipt of both radiation and proctectomy within 180 days of diagnosis. In addition, we explored associations between patient rurality and characteristics of surgery and radiation such as minimally invasive surgery (MIS) or intensity modulated radiation therapy (IMRT). Among 13,454 Medicare beneficiaries with nonmetastatic rectal cancer, 3926 (29.2%) underwent proctectomy within 180 days of being diagnosed with rectal cancer, and 1792 (13.3%) received both radiation and proctectomy. Small town/rural residence was associated with an increased likelihood of receiving both radiation and proctectomy within 180 days of diagnosis (adjusted subhazard ratio, 1.15; 95% CI, 1.02-1.30). Furthermore, small town/rural radiation patients were significantly less likely to receive IMRT (adjusted odds ratio, 0.62; 95% CI, 0.48-0.80) or MIS (adjusted odds ratio, 0.80; 95% CI, 0.66-0.97) than metropolitan patients. Although small town/rural Medicare beneficiaries were overall more likely to receive both radiation and proctectomy for their rectal cancer, they were less likely to receive preoperative IMRT or MIS as part of their treatment regimen. Together, these findings clarify that among Medicare beneficiaries, there appeared to be a similar utilization of radiation resources and time to radiation treatment regardless of rural/urban status.

Preoperative Dose-Escalated Intensity-Modulated Radiotherapy (IMRT) and Intraoperative Radiation Therapy (IORT) in Patients with Retroperitoneal Soft-Tissue Sarcoma: Final Results of a Clinical Phase I/II Trial.

To report the final results of a prospective, one-armed, single-center phase I/II trial (NCT01566123). Between 2007 and 2017, 37 patients with primary or recurrent (N = 6) retroperitoneal sarcomas were enrolled. Treatment included preoperative IMRT of 45-50 Gy with a simultaneous integrated boost of 50-56 Gy, surgery and IORT. The primary endpoint was local control (LC) at 5 years. The most common histology was dedifferentiated liposarcoma (51%), followed by leiomyosarcoma (24%) and well-differentiated liposarcoma (14%). The majority of lesions were high-grade (FNCLCC G1: 30%, G2: 38%, G3: 27%, two missing). Five patients were excluded from LC analysis per protocol. The minimum follow-up of the survivors was 62 months (median: 109; maximum 162). IORT was performed for 27 patients. Thirty-five patients underwent gross total resection; the pathological resection margin was mostly R+ (80%) and, less often, R0 (20%). We observed 10 local recurrences. The 5-year LC of the whole cohort was 59.6%. Eleven patients received a dose > 50 Gy plus IORT boost; LC was 64.8%; the difference, however, was not significant (p = 0.588). Of 37 patients, 15 were alive and 22 deceased at the time of final analysis. The 5-year OS was 59.5% (68.8% per protocol). The primary endpoint of a 5-year LC of 70% was not met. This might be explained by the inclusion of recurrent disease and the high rate of G3 lesions and leiomyosarcoma, which have been shown to profit less from radiotherapy. Stratification by grading and histology should be considered for future studies.

Preliminary Results of Phase II Study on Preoperative Intensity-Modulated Radiotherapy with Concurrent Tyrosine Kinase Inhibitor for Patients with Non-Metastatic Extremity and Trunk Soft Tissue Sarcoma

<h3>Purpose/Objective(s)</h3> Preoperative radiotherapy (RT) is one of the recommended treatments for primary extremity and trunk soft tissue sarcoma, however, the pathological remission is relatively low, and survival is not improved. We hypothesized that the addition of tyrosine kinase inhibitor (TKI) will improve the pathological remission rate without significant increase of major wound complications (MWCs). <h3>Materials/Methods</h3> Two phase II study were initiated in our center. Primary or recurrent non-metastatic extremity or trunk soft tissue sarcoma was enrolled. Patients received preoperative intensity-modulated radiotherapy (IMRT) of 50Gy in 25 fractions with concurrent and sequential Anlotinib (12 mg QD for 2 weeks, 3 cycles in total) or Apatinib (500 mg QD, 5 days per week, for 9 weeks in total), followed by wide resection. NCI-CTC 5.0, RECIST 1.1 criteria, and EORTC-STBSG criteria was used to evaluate acute toxicities, clinical response and pathological grading. The primary endpoint was defined as MWCs as per the SR2 criteria within 4 months post-surgery. <h3>Results</h3> From Jul 2020 to Dec 2021, 31 patients were enrolled and completed RT. The median onset age is 55 (22-82) years old. There are 26 and 5 patients with primary untreated and locally relapsed disease, respectively. The median tumor size is 10.5 (3.7-19.5) cm, with 23 patients (74.2%) larger than 8cm. Twenty-seven tumors (87.1%) were evaluated as unresectable or borderline resectable, which was defined as impossible or difficult to conserve limb with non-R2 wide resection. There were 21, 9 and 1 patients having Anlotinib, Apatinib and none, respectively. All except 5 took TKI as per protocol, with 4 patients having dose reduction due to Grade 3 toxicities. The observed ≥Grade 3 toxicities are: hypertension in 4 patients (19.1%) in Anlotinib group and 2 patients (22.2%) in Apatinib group, and one Grade 4 hepatotoxicity in Apatinib group (11.1%). There are 14 (14/30, 46.7%) and 16 patients (16/30, 53.3%) who achieved partial response (PR) and SD as per RECIST 1.1 criteria at 1-month post-radiotherapy, respectively. All the patients who had PR had obvious tumor shrink at the first 1 to 2 weeks during radiotherapy. Six out of 24 patients (25%) who underwent wide resection with at least 6 weeks follow-up had MWCs, with all in lower extremity. There were 4 (4/26, 15.4%), 3 (3/26, 11.5%) and 3 (3/26, 11.5%) patients achieving pathological Grade A, B, and C remission as per EORTC-STBSG criteria, respectively. All the 22 patients with unresectable or borderline resectable tumor had non-R2 limb-conserving wide resection, with 18 R0 and only 4 R1 resection. <h3>Conclusion</h3> For patients with non-metastatic extremity or trunk primary sarcoma, the combination of TKI and pre-operative RT is safe and well-tolerated, and achieve favorable clinical and pathological response. The earlier response with addition of TKI made more patients with unresectable or borderline resectable tumor completely resected by limb-conserving wide resection. NCT05167994, NCT05235100

Feasibility of Preoperative Dose-Painting Intensity Modulated Radiation Therapy (IMRT) for Borderline-Resectable Primary Retroperitoneal Sarcoma.

The role of radiation therapy (RT) in resectable retroperitoneal sarcoma (RPS) remains controversial; however, preoperative RT may play an important role in borderline-resectable (at risk of R2 resection) disease. We evaluated the outcome of such patients treated with preoperative dose-painting IMRT followed by planned resection. Between January 2001 and December 2017, 30 patients with borderline-resectable primary nonmetastatic RPS (after multidisciplinary review) received preoperative dose-painting IMRT in this retrospective cohort study. Median follow-up for all patients was 32 months. Median dose to the whole tumor/high-risk margin was 50.4 Gy/60.2 Gy. Sixteen patients were female, 24 were >50 years. Median tumor size was 9.2 cm. After RT, 6 did not have surgery. Of the 24 who were explored, 20 underwent complete gross resection. During RT, 7 of 30 patients developed acute grade 2+ toxicities: 5 fatigue, 1 nausea and vomiting, and 1 cystitis. RT was completed in 29 of 30 patients. Postoperatively, 12 of 20 patients developed grade 2+ complications: 2 gastropathy, 5 intraabdominal collections requiring drainage, 1 retroperitoneal bleed, and 3 delayed wound healing. Late grade 2+ toxicity was observed in 3 of 20 patients: 1 lymphedema with recurrent cellulitis, 1 chronic diarrhea, 1 gastrointestinal bleeding from anastomosis requiring transfusions, and 2 renal insufficiency. In those who underwent complete gross resection (n = 20, median follow-up 47 months), the 5-year local control was 57%, and overall survival was 46%. Preoperative dose-painting IMRT given to borderline-resectable RPS rendered 67% of patients resectable, provided a 5-year local control rate of 57%, which is similar to those with resectable disease, and had an acceptable morbidity profile.

Hyperfractionation versus Conventional Fractionation of Preoperative Intensity-Modulated Radiotherapy with Oral Capecitabine in Locally Advanced Mid-Low Rectal Cancer: A Propensity Score Matching Study.

Purpose In theory, the hyperfractionated radiotherapy can enhance biological effect dose against tumor and alleviate normal tissue toxicity. This study is to assess the efficacy and safety of preoperative hyperfractionated intensity-modulated radiotherapy (IMRT) with oral capecitabine in patients with locally advanced rectal cancer (LARC). Methods We retrospectively screened patients with LARC from January 2015 to June 2016. Patients that received hyperfractionated IMRT or conventional fractionated IMRT were eligible in the hyperfractionation (HF) group or conventional fractionation (CF) group, respectively. The primary outcome was the complete response rate. Secondary outcomes included toxicity, postoperative complications, anus-reservation operation rate, local recurrence and distant metastases rate, overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). Results 335 patients were included in the analysis. The complete response rate for the hyperfractionated and conventional fractionated IMRT was 20.41% vs. 23.47% (P = 0.583). The anus-reservation operation rate was 68.37% vs. 65.31% (P = 0.649). There were no cases of grade 4 toxicity during radiotherapy; the rate of grade 3 toxicity and postoperative complications was both comparable between groups. However, in the CF group, more patients had a second operation due to complications (0.0% vs. 5.68%, P = 0.011). The cumulative local regional recurrence and distant metastases rates of the HF group and CF group were 5.10% vs. 9.18% (P = 0.267) and 22.45% vs. 24.49% (P = 0.736), respectively. The 5-year OS, CSS, and DFS in the HF group and CF group were 86.45% vs. 73.30% (P = 0.503), 87.34% vs. 75.23% (P = 0.634), and 70.80% vs. 68.11% (P = 0.891), respectively. Conclusions The preoperative hyperfractionated IMRT with oral capecitabine, with an acceptable toxicity and favorable response and survival, could reduce the rate of secondary surgery.

Dose-escalated intensity modulated radiation therapy in patients with locally-advanced vulvar cancer - does it increase response rate?

PurposeGOG 205 safely increased clinical (cCR) and pathologic complete response (pCR) in locally-advanced vulvar cancer through dose escalation using three-dimensional radiotherapy (RT). The aim of this study is to assess the response of dose-escalated intensity modulated radiotherapy (IMRT) in locally-advanced vulvar cancer. MethodsA retrospective review of patients treated with dose-escalated (≥ 55Gy) IMRT from 2012 to 2018 for locally-advanced vulvar cancer was performed. Patients treated with preoperative or definitive intent were included. Rates of cCR and pCR were assessed, and predictors of disease-free survival (DFS) were analyzed using the Kaplan Meier method with log rank test between groups and a parsimonious multivariate Cox model. ResultsMedian dose to the vulva was 66.0 Gy (Interquartile Range [IQR]: 66.0–68.0) for definitive and 59.4 Gy (IQR: 58.0–59.4) for preoperative IMRT. The overall rates of cCR and pCR were 76% and 70%, respectively. DFS at two years was 65% (95% Confidence Interval [CI] 50–80%) for all patients, 81% (95% CI 63% - 98%) for definitive IMRT, and 55% (95% CI 35% - 76%) for preoperative IMRT. On multivariate analysis, cCR predicted for disease-free survival (HR 0.21; 95% CI 0.06–0.76; p = 0.02), and pCR predicted for OS (HR 0.12; 95% CI 0.02–0.60; p = 0.01). Grade 3 acute and late RT toxicity was seen in 14 (29%) and 3 (6%) of patients, respectively. ConclusionDose-escalated IMRT for locally-advanced vulvar cancer is well tolerated, with rates of cCR and pCR that compare favorably with published data.

Dose-Escalated Intensity Modulated Radiation Therapy in Patients with Locally Advanced Vulvar Cancer- Does It Increase Response Rate?

The management for locally-advanced vulvar cancer includes preoperative and definitive chemoradiotherapy. By increasing dose from 47.6Gy to 57.6Gy, GOG 205 safely increased clinical (cCR) and pathologic complete response (pCR) to 64% and 50% from 48% and 31% in GOG 101. Intensity modulated radiotherapy (IMRT) has improved the tolerability of radiotherapy in vulvar cancer, such that the ongoing GOG 0279 is examining further dose-intensification to 64Gy with concurrent gemcitabine and cisplatin. The aim of the current study is to assess the response of dose-escalated IMRT in locally-advanced vulvar cancer. We performed a retrospective review of patients treated with dose-escalated (≥54Gy) IMRT from 2012-2018 for locally-advanced vulvar cancer. Patients treated with preoperative (n=30, 67%) or definitive intent (n=15, 33%) were included, while patients treated with adjuvant radiotherapy were excluded. Concurrent chemotherapy with weekly cisplatin (40mg/m2) was administered in 93%. Median dose to the vulva was 66.8 Gy (IQR: 66.0 Gy to 68.0 Gy) for definitive and 59.4 Gy (IQR: 58.0 Gy-61.2 Gy) for preoperative IMRT. Toxicity was graded using CTCAE v4.03. Predictors of disease free survival (DFS) were analyzed using the Kaplan Meier method with log rank test between groups and a parsimonious multivariate Cox multivariate model. p16 status was not analyzed as a variable, due to missing data for p16 in 69%. Of the included 45 patients: median age was 67 years, 60% were ≥ cT2, 53% were node-positive on PET imaging, and 57% were ≥ FIGO Stage IIIA. The overall rate of cCR was 78%, with a pCR rate for preoperative patients of 63%. At a median follow-up of 18 months (IQR: 7.7 – 33.7), the 2-year DFS was 65% (95%CI 49%-81%) for all patients, 84% (95%CI 62%-100%) for definitive IMRT, and 58% (95%CI 39%-78%) for preoperative IMRT. pCR was a significant predictor of DFS on both univariate [2-year DFS 83% (95%CI 65%-100%) versus 21% (95%CI 0%-46%), p <0.01] and on multivariate analysis (HR 0.28, 95% CI 0.08-0.96). There was no significant difference in DFS by RT dose, age, clinical nodal status, SUV, or presence of lichen sclerosis on multivariate analysis. Median treatment duration was 46 days (IQR: 45-50 days), with a treatment break required in 4 patients, 3 for reasons unrelated to RT and 1 for febrile neutropenia. Grade 3 acute RT toxicity was seen in 14 (31%) patients and consisted mainly of radiation dermatitis, pain, and GI. Grade 3 late RT toxicity was seen in 3 (7%) of patients: vaginal stricture (n=2) and perineal pain (n=1). Dose-escalated IMRT for locally advanced vulvar cancer was well tolerated with acceptable acute and chronic effects, with minimal treatment interruptions. cCR and pCR rates compared favorably with published data. pCR is a strong predictor of DFS and may serve as a viable endpoint for future clinical trial design in locally-advanced vulvar cancer.

Preoperative Intensity Modulated Radiation Therapy Compared to Three-Dimensional Conformal Radiation Therapy for High-Grade Extremity Sarcomas in Children: Analysis of the Children's Oncology Group Study ARST0332

For pediatric patients with large, high-grade, extremity nonrhabdomyosarcoma soft-tissue sarcomas, preoperative radiation therapy (RT) provides the opportunity for smaller radiation fields and tumor shrinkage resulting in less extensive surgery. The potential disadvantage is an increased risk of wound complications after surgery compared with rates after postoperative chemoradiation. We assessed the impact of preoperative RT technique on target coverage in relationship to dose to skin and adjacent joints to determine whether acute wound complications and late musculoskeletal injury might be influenced by treatment technique. Of 550 eligible patients <30years of age, 200 were enrolled in arm D of ARST0332 and received neoadjuvant ifosfamide/doxorubicin, then chemoradiotherapy (45Gy and ifosfamide) and surgery followed by postoperative RT if gross or microscopic positive surgical margins. One-hundred thirteen patients had extremity nonrhabdomyosarcoma soft-tissue sarcomas, of which 56 patients had preoperative RT plans for digital review. The doses to the target volume, skin (surface to 5mm depth), adjacent joint, and extremity diameter were analyzed with respect to RT technique. Thirty-eight patients (65%) received 3-dimensional conformal RT (3D-CRT) and 18 (32%) received intensity modulated RT (IMRT). There was no difference in clinical target volume (CTV) size between groups (P=.920); however, IMRT plans had improved CTV coverage to 100% of the prescription dose compared with 3D-CRT plans (median CTV coverage, 92.7% vs 98.6%; P=.011). In patients without target overlap with the skin, IMRT use was associated with reduced percent volume of skin receiving 45Gy or more (V45Gy) compared with 3D-CRT (median, 1.6% vs 6.3%, respectively; P=.005). IMRT was also associated with reduced V45Gy to the adjacent joint compared with 3D-CRT (median, 1.1% vs 13.2%; P=.018). Preoperative IMRT may improve CTV coverage and reduce the volume of skin and adjacent joint treated to high doses. Future studies should assess whetherthese dosimetric findings produce differences in clinical and toxicity outcomes.

Preoperative IMRT for soft-tissue sarcoma of the extremities and trunk: low rate of wound complications

Background: The Canadian prospective randomized NCIC SR2 trial tested the sequence of radiation and surgery for extremity soft-tissue sarcoma. The trial was conducted in the era before intensity-modulated radiation therapy (IMRT) was clinically available. Similar disease control after preoperative and postoperative non-IMRT was found. However, the preoperative non-IMRT arm showed significantly less (persisting) late-term effects but increased (transient) wound complication rates compared to the postoperative non-IMRT arm (35% vs. 17%, P = 0.01). Consequently based on these results, preoperative radiation therapy was considered the preferred approach. Currently IMRT, with its option for highly conformal dose distribution that translates into better normal tissue sparing, is used as the general standard for sarcoma radiation therapy in most patients. Our hypothesis was that a lower wound complication rate after preoperative radiation therapy might be achievable in the IMRT era. Methods: We prospectively assessed our preoperative IMRT cohort (n=67 consecutive patients) treated between March 2008 and March 2016 with respect to wound complication rates. Results: Fourteen of 67 (21%) externally referred patients with recurrent (n=1) or incompletely resected disease (n=13), and 53 treatment-naive patients underwent planned preoperative radiation after core biopsy. After mean/median 7.3/7 wk (3-12 wk), complete tumor resection was performed. Secondary revision was required in five of 67 (i.e., wound complication rate of 7%). Two local failures were observed so far. Conclusions: The presented results support our hypothesis that preoperative IMRT may lead to a reduced wound complication rate compared to that after postoperative and mainly preoperative non-IMRT techniques.

Efficacy evaluation of preoperative intensity-modulated radiotherapy combined with concurrent chemotherapy in patients with locally advanced rectal cancer

Objective To evaluate the efficacy and adverse reactions of preoperative intensity-modulated radiotherapy (IMRT) combined with mFOLFOX6 chemotherapy regimen for locally advanced rectal cancer (LARC). Methods A total of 86 patients with LARC who received preoperative IMRT combined with chemotherapy in Shanxi Provincial Cancer Hospital from June 2010 to December 2012 were enrolled. The patients were randomly divided into 2 groups according to the random number table method. Forty-six patients were treated with mFOLFOX6 regimen (mFOLFOX6 group) and 40 patients were treated with fluorouracil (5-Fu) single drug injection (5-Fu group). The total dose of IMRT target region was 45-54 Gy, 25 times in total. Short-term efficacy, adverse reactions, survival and metastasis were evaluated respectively. χ2 test or Fisher test were used to compare the count variable. Kaplan-Meier method was used to calculate the survival rates and Log-rank was used to detect. Results The total follow-up rate was 97.67% (84/86). There were no statistical differences in the rate of resection (93.5% vs. 80.0%), pathological complete remission (pCR) rate (6.5% vs. 0) and 3-year overall survival (OS) rate (87.0% vs. 70.0%) in the mFOLFOX6 group and 5-Fu group respectively (all P > 0.05). Down-staging rate, 3-year disease free survival (DFS) rate and distant metastasis free survival (DMFS) rate in the mFOLFOX6 group were significantly higher than those in 5-Fu group (58.7% vs. 32.5%, 79.1% vs. 50.0%, 89.1% vs. 72.5%, all P < 0.05). Conclusions Preoperative IMRT combined with mFOLFOX6 regimen can decrease the preoperative staging of LARC patients, improve 3-year DFS rate and DMFS rate. The adverse reactions may increase, but it is tolerant. Key words: Rectal neoplasms; Radiotherapy, intensity-modulated; Drug therapy, combination

Preoperative Intensity-Modulated Radiation Therapy Compared to Three-Dimensional Conformal Radiation Therapy for High Grade Extremity Sarcomas in Children: An Analysis of Children's Oncology Group (COG) Study ARST 0332

One of the potential disadvantages of neoadjuvant chemoradiation therapy for high grade extremity soft tissue sarcomas (STS) is an increased risk of peri-operative wound complications. In adults, studies have demonstrated reduced radiation dose to the skin and subcutaneous soft tissues may decrease the acute wound complication rate and lead to better limb function. Intensity modulated radiotherapy (IMRT) allows delivery of dose to the target volume with the potential advantage of highly conformal therapy to reduce dose to subcutaneous tissues thus limiting dose to the skin. The purpose of this study was to assess tumor coverage and skin dose in pediatric patients treated with IMRT vs. 3D conformal radiation therapy (3D-CRT) on ARST 0332. Of the 551 eligible patients, 200 were enrolled in Arm D of ARST 0332 in which patients <30 years of age were treated with neoadjuvant ifosfamide/doxorubicin chemotherapy and 45 Gy RT, then surgery, and an RT boost based on margins. A total of 121 RT plans of patients were available for review through remote access of the Imaging and Radiation Oncology Core (IROC) Rhode Island database. Of these, 56 RT plans for patients with extremity STS were reviewed to evaluate the dose delivered to the clinical target volume (CTV) and skin (contoured from the surface to a depth of 5 mm). Of the 56 pediatric patients with extremity STS with RT plans available for review, 38 (65%) were treated with 3D-CRT and 18 (32%) with IMRT. There was no difference in distribution of site treated with IMRT vs. 3D-CRT (upper leg: 53% vs. 50%; knee: 16% vs. 17%; lower leg: 11% vs. 17%; lower arm: 11% vs. 17%, IMRT vs. 3D-CRT, respectively) with the exception of 0% vs. 11% of patients treated with IMRT vs. 3D-CRT to the upper arm. There was no difference in CTV volume between groups of patients treated with IMRT (median 1027 cc, range 66-2867 cc) or 3D-CRT (median 647 cc, range 30-4854 cc) (P = 0.920); however, patients treated with IMRT had significantly improved CTV coverage with 100% of the prescription dose compared to those receiving 3D-CRT (median CTV coverage, 95% vs. 87% respectively, P = 0.011). In patients without skin bolus, the percentage of skin receiving 45 Gy or more was significantly lower in patients treated with IMRT compared to 3D-CRT (mean percentage, 3% vs. 8% respectively, P = 0.039). Pre-operative IMRT compared to 3D-CRT may result in improved RT target coverage with reduced dose to the skin. Future studies are important to assess if this lower skin dose translates to reduced wound complications and/or improved limb function.

Preoperative intensity-modulated radiotherapy with a simultaneous integrated boost combined with Capecitabine in locally advanced rectal cancer: short-term results of a multicentric study

BackgroundPreoperative radiotherapy (RT) in combination with fluoropyrimidine-based chemotherapy (CT) is the standard of care in patients with locally advanced, T3-T4 N0–2, rectal cancer (LARC). Given the correlation between RT dose-tumor response and the prognostic role of the tumor regression grade (TRG), treatment intensification represents an area of active investigation. The aim of the study was to analyze the role of RT dose-intensification in the preoperative treatment of LARC in terms of feasibility, efficacy and toxicity.MethodsWe retrospectively analyzed patients with LARC treated with intensity-modulated radiotherapy (IMRT) and simultaneous integrated boost (SIB) at five Italian radiation oncology centers. Concurrent Capecitabine was administered. Treatment response was evaluated in terms of disease down-staging and TRG. Acute toxicity was evaluated according to the CTC-AE 4.0 scale.ResultsA total of 76 patients were identified for this analysis. A dose of 45 Gy was prescribed to the entire mesorectum and pelvic lymph nodes with a median SIB dose of 54 Gy (range 52.5–57.5) to the tumor and corresponding mesorectum. Overall, 74/76 (97.4%) patients completed the planned RT, whereas 64/76 (84.2%) patients completed the prescribed CT. Eight (10.5%) patients developed grade 3–4 acute toxicity. Overall, 72/76 patients underwent surgery. The tumor and nodal down-staging was documented in 51 (70.8%) and 43 (67%) patients, respectively. Twenty (27.8%) patients obtained a pathologic complete response. Surgical morbidity was reported in 13/72 patients (18.1%).ConclusionsAlthough retrospective in design, this study indicates that IMRT-SIB with a dose range of 52.5–57.5 Gy (median 54 Gy) and concomitant Capecitabine appears feasible, well tolerated and effective in terms of disease down-staging and pathological complete response. Long-term toxicity and the impact on disease control and patient survival will be evaluated with a longer follow-up time.Trial registrationNA

Intensity modulated radiation therapy for squamous cell carcinoma of the vulva: Treatment technique and outcomes

ObjectiveThe objective of this study was to present the treatment technique and evaluate clinical outcomes after intensity modulated radiation therapy (IMRT) for vulvar cancer. Methods and materialsThis retrospective study included 39 patients with squamous cell carcinoma of the vulva treated with IMRT from 2005 to 2015. There were 21 patients treated with postoperative IMRT, 13 with definitive IMRT, and 5 with preoperative IMRT. Tumor staging was Federation of Gynecology and Obstetrics stage I in 6, stage II in 7, stage III in 19, and stage IV in 7 patients. Concurrent chemotherapy was administered to 14 patients. Brachytherapy was delivered in 8 patients. ResultsThe median follow-up was 34 months (range, 3.3-71). Median IMRT dose to patients receiving pre- or postoperative IMRT was 5040 cGy (range, 5040-6080). Median combined IMRT and brachytherapy dose to gross tumor was 7000 cGy (range, 5040-7520) in those treated with definitive RT. The 3-year locoregional control (LRC) and overall survival for those receiving postoperative RT were 89% and 67%, respectively. The 3-year LRC and overall survival for those receiving definitive IMRT were 42% and 49%, respectively. In patients receiving definitive or neoadjuvant IMRT, 69% had complete clinical response and 44% had complete pathologic response. The actuarial 3-year inguinal recurrence rate was 7%. There were no acute grade 3-4 hematological, gastrointestinal, or genitourinary toxicities. There were no late grade 3-4 gastrointestinal or genitourinary toxicities. ConclusionsIMRT for vulvar cancer is associated with high rates of LRC in the postoperative setting and limited radiation-related toxicity. Durable LRC of disease after definitive IMRT remains challenging, and several refinements to our treatment technique are suggested.

MTE29.02 Advances in Malignant Pleural Mesothelioma

MTE29.02 Advances in Malignant Pleural Mesothelioma

A phase II trial of preoperative concurrent chemotherapy and dose escalated intensity modulated radiotherapy (IMRT) for locally advanced rectal cancer.

Objectives: To determine the pathological response rates and toxicity and in patients with locally advanced rectal cancer treated with concurrent capecitabine and dose escalated intensity modulated radiotherapy (IMRT)Methods: Patients with stage II or III adenocarcinoma of the rectum were treated with preoperative concurrent capecitabine and IMRT. Dose of capecitabine was 825mg/m2, 5 days a week for 5 weeks. IMRT was used to deliver a dose of 45Gy in 25 fractions (1.8Gy per fraction daily, 5 days a week over 5 weeks) to the regional lymphatics and areas at risk of harbouring microscopic disease. A concomitant synchronous integrated boost (SIB) to the gross tumour with a margin to a total dose of 55Gy in 25 fractions was also delivered in the same period. TME surgery was performed 8 weeks after preoperative therapy. The primary endpoint is pathological complete response rate (pCR) and the secondary endpoint was downstaging rates, Sphincter preservation rates (SPR), disease free survival (DFS) at 2 years and toxicity graded using the CTCAE v3.0.Results: Twenty three patients were enrolled. Three were not evaluable; one did not complete treatment due to logistic issues and two declined surgery. The remaining 20 patients completed preoperative chemoIMRT followed by TME surgery.At a median follow-up of 38.2 months (17.5-53.2 months), 90% (18 of 20) patients were alive. The 2 year overall survival and DFS were 90% and 90% respectively. 35%(7/20) of patients had a pCR. 65% (13 of 20) patients had successful downstaging of their rectal tumours. There was no local recurrence. Sphincter preservation rate was 85%. Treatment was well tolerated with only one patient (5%) having Grade 3 radiation proctitis.Conclusions: Preoperative concurrent capecitabine and dose escalated IMRT is well tolerated and results in high rates of pCR. A randomized trial comparing this regimen with standard 3D conformal chemoradiotherapy is warranted.

The impact of 3D conformal radiotherapy versus intensity-modulated radiotherapy on post-operative wound complications in soft tissue sarcomas of the extremity and chest-wall

Background Pre-operative radiotherapy (RT) followed by limb-sparing resection is commonly used to treat soft tissue sarcomas (STS) of the extremity and chest-wall; however, this is associated with an increased risk of post-operative wound complications (WCs) compared to adjuvant RT. The use of intensity-modulated radiotherapy (IMRT) in STS has been investigated; however, the impact on WC is sparsely reported. In this study, we assess the rates of WC in patients who underwent pre-operative 3D conformal RT (3D CRT) versus IMRT followed by surgery for STS.

Acute Toxicity and Tumor Response in Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy With Shortening of the Overall Treatment Time Using Intensity-Modulated Radiation Therapy With Simultaneous Integrated Boost: A Phase 2 Trial

This phase 2 study investigated the efficacy and safety of preoperative intensity modulated radiation therapy with a simultaneous integrated boost (IMRT-SIB) without dose escalation, concomitant with standard capecitabine chemotherapy in locally advanced rectal cancer. Between January 2014 and March 2015, 51 patients with operable stage II-III rectal adenocarcinoma received preoperative IMRT with pelvic dose of 41.8Gy and simultaneously delivered 46.2Gy to T2/3 and 48.4Gy to T4 tumor in 22 fractions, concomitant with capecitabine, 825mg/m2/12hours, including weekends. The primary endpoint was pathologic complete response (pCR). Fifty patients completed preoperative treatment according to the protocol, and 47 underwent surgical resection. The sphincter preservation rate for the low rectal tumors was 62%, and the resection margins were free in all but 1 patient. Decrease in tumor and nodal stage was observed in 32 (68%) and 39 (83%) patients, respectively, with pCR achieved in 12 (25.5%) patients. There were only 2G≥ 3 acute toxicities, with infectious enterocolitis in 1 patient and dermatitis over the sacral area caused by the bolus effect of the treatment table in the second patient. Preoperative IMRT-SIB without dose escalation is well tolerated, with alow acute toxicity profile, and can achieve a high rate of pCR and downstaging.