RT Field Research Articles

Clinical Outcomes With Dose Escalation Using Intensity Modulated Radiation Therapy for Node-Positive Endometrial and Cervical Cancer

To determine rates of nodal control and survival in patients with endometrial or cervical cancer treated with intensity modulated radiation therapy (IMRT) with dose escalation to nodal regions. Records of 71 gynecologic-cancer patients (pts) treated with IMRT between November 2005 and April 2011 were reviewed. Thirty-two pts received IMRT with a boost to gross disease with curative intent and constitute the study population. Twenty-two pts (68%) had endometrial cancer (FIGO stage: IIIB=1, IIIC=9 and recurrent=12) and 10 pts (31%) had cervical cancer (FIGO stage: IB2=1, IIA =1, IIB=5, IIIB=1 and recurrent=2). The first course RT treatment field was pelvic in 7 pts, paraortic in 4, extended field in 20 and 1 pt received whole-abdominal RT. The areas of nodal boost included pelvic nodes in 12 pts (38%), paraortic nodes (PAN) in 13 (41%) and both pelvic and PAN in 7 pts (21%). The first course RT dose was 45 Gy for pelvic and paraortic areas. The median total dose to gross nodal disease was 63 Gy (range, 54 to 68.4 Gy); it was 61 Gy for cervical cancer and 63 Gy for endometrial cancer. Thirty pts (93%) received chemotherapy. The rates of local control, progression-free survival (PFS) and overall survival (OS) were determined using the Kaplan-Meier method. Median follow-up time was 21.8 months (range, 5.6-64.2 months). The mean lymph node axial dimension was 2.5 cm (range, 1 to 6.9 cm). The overall response rate was 87%. Five pts (15%) developed nodal relapse (1/10 cervical cancers, 4/22 endometrial cancers). Four of the 5 relapses were infield (2 pelvic node, 1 common iliac, 1 PAN) and 1 was in the primary RT field outside the boost field (common iliac node after boost to PAN). For the 5 nodal relapses after RT, the mean relapsed nodal size was 2.4 cm (range, 1.4-4.2) and the mean RT dose was 64.5 Gy (range, 61.2-68.4). All pts with infield relapse had received more than 63 Gy. The median time to first relapse was 9.6 mos (range, 5.6-46.6). Four of 5 nodal relapses occurred within 1.5 years. Three of 5 pts with nodal relapse had distant metastasis (2 concurrent and 1 subsequent). Seven pts (2 cervical and 5 endometrial cancers) developed distant metastasis without nodal relapse. The 2-year rate of nodal control was 85%, PFS was 69% and OS was 81%. Acute grade 3 toxicity was: 2 gastrointestinal, 1 genitourinary and 11 hematologic. Four pts experienced grade 3 late toxicity (1 cystitis, 1 colitis and 4 anemia). There was no grade 4-5 toxicity. The 2-year actuarial grade 3 late toxicity rate was 14%. Using IMRT for definitive treatment with dose escalation to gross nodal disease for endometrial and cervical cancer is feasible with acceptable toxicity and is associated with a high survival rate.

Patterns of failure after multimodal treatments for high-grade glioma: effectiveness of MIB-1 labeling index

BackgroundThe purpose of the present study was to analyze the recurrence pattern of high-grade glioma treated with a multimodal treatment approach and to evaluate whether the MIB-1 labeling index (LI) could be a useful marker for predicting the pattern of failure in glioblastoma (GB).Methods and materialsWe evaluated histologically confirmed 131 patients with either anaplastic astrocytoma (AA) or GB. A median dose was 60 Gy. Concomitant and adjuvant chemotherapy were administered to 111 patients. MIB-1 LI was assessed by immunohistochemistry. Recurrence patterns were categorized according to the areas of recurrence as follows: central failure (recurrence in the 95% of 60 Gy); in-field (recurrence in the high-dose volume of 50 Gy; marginal (recurrence outside the high-dose volume) and distant (recurrence outside the RT field).ResultsThe median follow-up durations were 13 months for all patients and 19 months for those remaining alive. Among AA patients, the 2-year progression-free and overall survival rates were 23.1% and 39.2%, respectively, while in GB patients, the rates were 13.3% and 27.6%, respectively. The median survival time was 20 months for AA patients and 15 months for GB patients. Among AA patients, recurrences were central in 68.7% of patients; in-field, 18.8%; and distant, 12.5%, while among GB patients, 69.0% of recurrences were central, 15.5% were in-field, 12.1% were marginal, and 3.4% were distant. The MIB-1 LI medians were 18.2% in AA and 29.8% in GB. Interestingly, in patients with GB, the MIB-1 LI had a strong effect on the pattern of failure (P = 0.014), while the extent of surgical removal (P = 0.47) and regimens of chemotherapy (P = 0.57) did not.ConclusionsMIB-1 LI predominantly affected the pattern of failure in GB patients treated with a multimodal approach, and it might be a useful tool for the management of the disease.

Impact of a second FDG PET scan before adjuvant therapy for the early detection of residual/relapsing tumours in high-risk patients with oral cavity cancer and pathological extracapsular spread

Extracapsular spread (ECS) to the cervical lymph nodes is a major adverse prognostic factor in oral cavity squamous cell carcinoma (OSCC). We prospectively examined the value of FDG PET immediately before postoperative radiotherapy/concurrent chemoradiotherapy (pre-RT/CCRT PET) to detect residual/relapsing disease in the early postsurgical follow-up period in high-risk OSCC patients with ECS. We examined 183 high-risk OSCC patients with ECS who underwent preoperative FDG PET/CT for staging purposes. Of these patients, 29 underwent a second pre-RT/CCRT FDG PET/CT scan. The clinical utility of the second FDG PET/CT was examined using Kaplan-Meier curve analysis. Patients who underwent the second FDG PET/CT scan had baseline clinicopathological characteristics similar to those who did not undergo a second scan. Of the patients who underwent the second scan, seven (24 %) had unexpected, newly discovered lesions. Five eventually died of the disease, and two had no evidence of recurrence after a change in RT field and dose. In an event-based analysis at 2 months, rates of neck control (6/29 vs. 6/154, p = 0.001), distant metastases (3/29 vs. 4/154, p = 0.046), and disease-free survival (7/29 vs. 10/154, p = 0.003) were significantly higher in patients who received a second PET scan than in those who did not. The second pre-RT/CCRT PET scan was of particular benefit for detecting new lesions in OSCC patients with both ECS and lymph node standardized uptake value (SUV) of ≥ 5.2 in the first PET scan. The present findings support the clinical value of pre-RT/CCRT FDG PET for defining treatment strategy in OSCC patients with both ECS and high nodal SUV, even when FDG PET had already been performed during the initial staging work-up.

P3-13-04: Functional and Cosmetic Outcomes Following Post-Mastectomy Irradiation with Tissue Expander/Implant Reconstruction.

Abstract Purpose: To examine the rate of breast reconstruction failure and cosmetic outcomes following post-mastectomy radiation therapy (PMRT) with temporary tissue expander or implant in place. Methods and Materials: Ninety-four patients with 95 primary breast malignancies underwent mastectomy and immediate tissue expander reconstruction followed by PMRT. Ninety tissue expanders and five implants were irradiated. All patients received a dose of 5,400 cGy given in 180 cGy fractions. Twenty-one patients (22%) received tangents alone and seventy-four patients (78%) were treated with tangents and a supraclavicular field via a mono-isocentric technique. Bolus was used in 91 patients (96%). Eighty-eight patients (93%) received chemotherapy and 78 patients (82%) received endocrine therapy. Results: With a median follow up of 22.4 months, nineteen patients (20%) developed a reconstruction failure. Ten patients lost their tissue expanders with a median time to reconstruction failure of 7 months (range 3–9 months) while ten patients lost their permanent implant with a median time to loss of 19 months (range 9–31 months) following PMRT. The one and two-year actuarial rate of reconstruction failure was 11.2% and 24.9%, respectively. The most common cause of failure was infection (37%), followed by skin break down (21%), extrusion of expander or implant (16%), fibrosis/eschar (11%), trauma (11%) and pain (5%). Out of the 19 failures, eight patients were salvaged with an autologous flap reconstruction. Univariate analysis was performed to examine the association between age, chemotherapy, hormonal therapy, smoking status, hypertension, diabetes, menopause status, weight and the use of a third supraclavicular RT field on reconstruction failure. However no risk factors were found to be associated with reconstruction failure. In patients who did not have reconstruction failure, good/excellent cosmesis was observed in 79% of patients and fair/poor cosmesis was observed in 21% of patients. Conclusions: In our series of women with a high risk of recurrence, PMRT with a tissue expander in place followed by a prosthetic implant provides good cosmesis in the majority of women with an acceptable risk of expander or implant loss. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-13-04.

Chemoradiotherapy for locally advanced head and neck cancers: Two-year survival and toxicity outcomes from a regional cancer centre in UK.

e16020 Background: To evaluate the 2-year overall survival (OS), cause-specific survival and toxicities of locally advanced head and neck cancer patients treated with primary chemo-radiotherapy (CRT) over a two year period. Methods: Between June 2006 and May 2008, sixty patients with locally advanced head and neck cancers were treated (excluding skin and thyroid). Of these, seventeen (28.33%) were stage III, thirty nine (65%) were stage IVA and four (6.66%) were stage IVB. All received concurrent 3 weekly cisplatin (75-80 mg/m2) and radiotherapy dose of 66-70 Gy in 33-35 fractions, treated daily in three phases by conformal 3-dimensional CT-planning. Treatment response was assessed radiologically 3 months post primary CRT. Survival was calculated from the time of histological diagnosis and time to treatment tailure (TTF) from the completion of treatment. Results: The median age was 57 years (range 18-79) and M:F ratio was 3:1.The 2-year OS was 73.3 % and loco-regional control rate was 83.3 %. The treatment failure rate was 16.6 % (10/60 patients) with a median TTF of 5 months (range= 1 to 24 months). Sixteen patients (26.6%) died with in 2 years of treatment of which five (4%) died of progression from residual disease, six (4.8%) died of loco-regional recurrence and three (5%) died of distant recurrence. Rest of the three died of other causes and includes two (3.33%) from second primary (lung and oesophageal) cancers. The incidence of acute severe or persistent oral mucositis was 4% (RTOG grade 3) and none had grade 3/4 skin toxicity. The incidence of late toxicities was 4% for osteoradionecrosis (ORN) of the mandible, 3.2% for severe trismus and 2.4% had sinus/fistula formation. The incidence of severe oropharyngeal stenosis/total dysphagia was 3.2% and 3 patients (2.4%) were on long term (15-32 months) gastrostomy feeding tube for nutrition. One patient (0.8%) developed severe carotid artery disease in the RT field. None of the patients had treatment related death. Conclusions: Our results are on par with international standards published in the literature. This data will be followed up for long-term outcomes and can be used as a bench mark for comparison with current modern planning techniques like intensity modulated radiotherapy (IMRT).

Impact of tillage on solute transport in a loamy soil from leaching experiments

Soil tillage practices can affect water flow and solute transport processes dynamically in space and in time. However, the relationship between tillage practices and flow and transport in soils is not yet well understood. Within this paper, we analyze the short term impact of the conversion from conventional mouldboard ploughing (CT) to reduced disc harrowing (RT) on the solute transport process within a loamy soil. Solute breakthrough experiments at two flow rates were performed on 2 undisturbed lysimeter collected in a CT and RT field plot. Solute transport parameters were estimated using transfer function theory. Important differences in solute transport were observed between the RT and the CT treatments. The CT treatment exhibited a rapid, more homogeneous and less dispersive solute transport as compared to the RT treatment. These results are explained by the changes in soil structure due to tillage and compaction. The dominant transport was identified as being a stochastic-convective process in both lysimeters. The similarity of the mixing regime for the two soil columns can be explained by preferential solute trajectories activated within structural macropores as a result of the high flow rates applied. We show that the relationship between tillage practices and transport is complex, not only scale and time dependent but also influenced by the boundary conditions and tillage practices.

Development of a Novel Double-strand Break Repair Assay for High-throughput Small Molecule Screening in Glioma Cell Lines

Radioresistance is a key factor, which limits the efficacy of radiotherapy for the treatment of many cancers, and DSB repair pathways play a critical role in the protection of tumor cells from IR-induced killing. Malignant gliomas are thought to be particularly resistant to IR, as most tumor recurrences occur within the RT field, and dose escalation attempts have failed to yield improvements in local control. As such, significant effort has been focused on the development of small molecule radiosensitizers, which specifically target the two major DSB repair pathways, homologous recombination (HR), and non-homologous end joining (NHEJ).

Clinical Results of Image-Guided Deep Inspiration Breath Hold Breast Irradiation

To evaluate the feasibility, cardiac dose reduction, and the influence of the setup error on the delivered dose for fluoroscopy-guided deep inspiration breath hold (DIBH) irradiation using a cone-beam CT for irradiation of left-sided breast cancer patients. Nineteen patients treated according to the DIBH protocol were evaluated regarding dose to the ipsilateral breast (or thoracic wall), heart, (left ventricle [LV] and left anterior descending artery [LAD]), and lung. The DIBH treatment plan was compared to the free-breathing (FB) treatment planning and to the dose data in which setup error was taken into account (i.e., actual delivered dose). The largest setup variability was observed in the direction perpendicular to the RT field (μ = -0.8 mm, Σ = 2.9 mm, σ = 2.0 mm). The mean (D(mean)) and maximum (D(max)) doses of the DIBH treatment plan was significantly lower compared with the FB treatment plan for the heart (34% and 25%, p < 0.001), LV (71% and 28%, p < 0.001), and LAD (52% and 39.8%, p < 0.001). For some patients, large differences were observed between the heart D(max) according to the DIBH treatment plan and the actual delivered dose (up to 71%), although D(max) was always smaller than the planned FB dose (mean group reduction = 29%, p < 0.001). The image-guided DIBH treatment protocol is a feasible irradiation method with small setup variability that significantly reduces the dose to the heart, LV, and LAD.

Efficacy of Abbreviated Stanford V Chemotherapy and Involved Field Radiotherapy in Early Stage Hodgkin's Disease: Mature Results of the G4 Trial.

Abstract 1670Poster Board I-696The standard management for early stage Hodgkin's disease (HD) is combined modality therapy. In the G4 protocol, patients (pts) with non-bulky, supra-diaphragmatic stage I-IIA disease received 8 weeks of Stanford V chemotherapy + 30 Gy involved field radiotherapy (IFRT).87 pts were enrolled and treated between 4/1996 and 4/2001. Median age was 30 years (16-59) and stages were IA (n=23), IIA (n=64). Unfavorable risk factors were present in 47 patients (54%) according to German Hodgkin Study Group (GHSG) criteria (> 2 AA sites, ESR > 50 or EN involvement) and 38 (44%) according to EORTC criteria (> 3 AA sites, ESR > 50). Therapy was well tolerated with grade 3-4 non-hematologic toxic events in 7 % of pts. These included constipation (n=3), peripheral neuropathy (n=1), generalized weakness (n=2), chest pain (n=1), mylagias (n=1), abdominal pain (n=1) and an allergic reaction to etoposide (n=1). 42 patients received cytokine support for grade 3-4 neutropenia however only 2 pts developed fever with neutropenia. No cases of clinical bleomycin toxicity or radiation pneumonitis were observed. At a median follow-up of 9 (2-12) years, freedom from progression (FFP) and survival (OS) are 94% and 96% respectively. FFP was 100% for favorable and 89% for unfavorable patients by GHSG criteria (p=0.04) with no differences in OS (96.9% versus 95.7%). All relapses (n=5) occurred in the RT field: limited in 2 patients and combined with distant disease in 3 pts. All relapses were in “unfavorable” risk patients: 5 per GHSG and 4 per EORTC criteria. Secondary therapy included chemotherapy followed by high dose therapy and stem cell support (n=3) and ABVD (n=2). Three pts died, 2 due to disease progression after second-line therapy and one due to metastatic colon cancer. 5 patients developed a second cancer (2 breast, 2 melanomas at unirradiated sites and 1 colon cancer). The cases of breast cancer were considered unrelated to RT as both occurred within 5-years of therapy in women who were > 30 yrs at time of treatment. No secondary AML and no late cardiac or pulmonary toxicities have been observed.In conclusion, for pts with non-bulky stage I/II A HD, abbreviated Stanford V with 8 weeks of chemotherapy and 30 Gy IFRT is a safe and highly effective regimen. It is still too early to assess potential RT-related complications. Our outcomes in “unfavorable” stage I-IIA patients without bulky or symptomatic disease compare favorably with more intensive or prolonged regimens employed by the GHSG and EORTC. DisclosuresNo relevant conflicts of interest to declare.

Acute toxicity to the skin and mucosa of radiotherapy alone versus radiotherapy in combination with cetuximab or chemotherapy in patients with head and neck cancer

e17007 Background: To evaluate acute toxicity of the skin and mucosa in patients with head and neck cancer who received Radiotherapy alone (RT) or in combination with cetuximab (IRT) or chemotherapy (CRT). Methods: We retrospectively analyzed 204 patients with head and neck cancer, treated between 2006 and 2008. RT was combined with cetuximab (n = 57), or with platinum-based chemotherapy (n = 99), 48 patients received RT alone. We included 149 male and 55 female patients with a median age of 62 years (range 22–92). Median radiation dose was 66 Gy (range 26.4–71.6Gy). 126 patients received intensity modulated radiotherapy (IMRT), 78 patients had conventional RT. Toxicity was assessed according to CTCAE Version 3.0. Results: Median follow-up was 9 months (range 1–34). Acute grade 3 toxicity of the skin was observed in 26% of IRT, 0% of RT, and 7% of CRT patients. Typical appearance of grade 3 skin toxicity in IRT was a massive confluent epitheliolysis of the RT field. Grade 3 mucositis appeared in 21% of IRT-, 12.5% of RT-, and 16% of CRT-patients. Rates of skin toxicity grade 3 were 8% in patients with IMRT and 15% in patients with conventional RT. Grade 3 mucositis was seen in 22% of the IMRT-patients and 8% of the patients with conventional RT. Cetuximab did not lead to a higher rate of RT interruptions as compared to RT and CRT. Early intervention and supportive care in case of high grade toxicity was performed for all patients. 8 weeks after RT all patients showed recovery from toxicity. Conclusions: Higher toxicity to the skin and to the mucosa occurred in the IRT group, and seems to be a specific side effect in the treatment of head and neck cancer patients with concomitant cetuximab and RT. But severity of toxicity may also be influenced by other factors such as RT technique. IRT patients need close observation and early intervention in case of therapy induced toxicity in order to prevent RT interruption, which might limit the advantage of cetuximab. Longer follow-up is needed to evaluate outcome and late toxicity of the different treatment groups. [Table: see text]

Does Axillary Boost Increase Lymphedema Compared With Supraclavicular Radiation Alone After Breast Conservation?

To determine independent predictors of lymphedema (LE) after breast radiotherapy and to quantify added risks of LE from regional node irradiation (RNI). A total of 2,579 women with T1-2, N 0-3, M0 breast cancer treated with breast conservation between 1970 and 2005 were studied. A total of 2,169 patients (84%) received radiation to the breast (B), 226 (8.8%) to the breast and supraclavicular LNs (B+SC), and 184 (7.1%) to the breast, supraclavicular LNs, and a posterior axillary boost (B+SC+PAB). Median follow-up was 81 months (range, 3-271). Eighteen percent of patients developed LE. LE risks were as follows: 16% (B), 23% (B+SC), and 31% (B+SC+PAB) (p < 0.0001). LE severity was greater in patients who had RNI (p = 0.0002). On multivariate analysis, RT field (p < 0.0001), obesity index (p = 0.0157), systemic therapy (p = 0.0013), and number of LNs dissected (p < 0.0001) independently predicted for LE. In N1 patients, the addition of a SC to tangents (p < 0.0001) and the addition of a PAB to tangents (p = 0.0017) conferred greater risks of LE, but adding a PAB to B+SC RT did not (p = 0.8002). In the N2 patients, adding a PAB increased the risk of LE 4.5-fold over B+SC RT (p = 0.0011). LE predictors included number of LNs dissected, RNI, obesity index, and systemic therapy. LE risk increased when a SC or PAB were added in the N1 subgroup. In the N2 patients, a PAB increased the risk over B+SC. The decision to boost the axilla must be weighed against the increased risk of LE that it imposes.

Does conformal therapy improve dose distribution in comparison to old techniques in teleradiotherapy of cervical cancer patients?

Summary Background The use of a combined modality approach – chemotherapy and radiation therapy – in the treatment of patients with cervical cancer is associated with significant toxicity, mainly haematological and gastrointestinal. Conformal radiotherapy has the potential to deliver an adequate dose to the target structures while sparing the normal tissue. Both the radiation dose to the small bowel and the volume are factors known to influence the risk of complications. Aim The aim of this study was to determine whether the implementation of conformal modality can reduce the volume of normal tissue included in the RT field. Methods and Materials 14 cervical cancer patients (FIGO IIB and IIIB) treated with conformal radiotherapy concurrently with cisplatin (40 mg/m2) administration once a week were analyzed. According to ICRU 50 recommendations target volumes and the organs at risk were contoured on CT slices. For the gross tumour volume (GTV) the tumour of the uterus and cervix was traced. The clinical target volume (CTV) was defined as the vessels and lymph nodes from the obturator level to the aortic bifurcation, presacral region, and upper 1/3 of the vagina. The margin for planning target volume (PTV) was added. The normal tissue region included the small bowel, large bowel and bladder. Using a 3D system and multi-leaf collimator a four-field treatment plan was performed for each patient. All 14 patients were treated with radiotherapy using these conformal 3D plans. Additionally (just for study purposes) for each patient we prepared two simpler plans with (1) two-field: anterior-posterior (A-P) and posterior-anterior (P-A); and (2) four-field box techniques. Dose-volume histograms of target volumes and organs at risk were calculated for each three plans for every patient and compared. Analysis of variance was performed to compute the statistical significance. Results There is no statistical difference between doses received by target volumes – in each plan PTV is covered by the 95% isodose. Significantly different volumes of critical organs were included in the treatment field, depending on radiotherapy technique (conformal 3D method vs AP–PA two-field method): rectum 96.82% vs 38.23%, bowels 61.37% vs 30.79%. Conclusion These data suggest that implementation of conformal radiotherapy can reduce the irradiated volume in all the contoured critical organs, especially the bowels, compared to old techniques.

PD5-2-3: Translating research into routine clinical practice: image-guided lung stereotactic radiation therapy for unresectable patients with early stage lung cancer

Stereotactic Body Radiation Therapy (SBRT) has emerged as a non-invasive treatment option for unresectable early stage non-small cell lung cancer (NSCLC), delivering very high radio-ablative doses of RT to the primary tumor. To ensure efficacy of treatment and patient safety, high precision planning and careful treatment delivery under vigilant quality assurance are needed. We present the evolution of SBRT practice at Princess Margaret Hospital with an emphasis on accuracy of treatment set up and verification using image-guided techniques. From Oct 2004 to Feb 2007, we treated 46 patients (pts) with T1T2N0MO NSCLC with SBRT (48 tumors were treated). RT schedule for peripheral tumors was 60 Gy/3 fractions over 2 weeks (for 29 tumors, 12 of the pts were part of the RTOG 0236 phase II study). When organ at risk tolerance doses were not achievable, either 54 Gy/3 fr (3 pts) or 48 Gy/4 fr (10 tumors, all T1) was employed. Central tumors were treated with a lower dose of 50 Gy/10 fr schedule (6 pts). 4DCT simulation was acquired in all but 9 pts who were too large for the scanner. All tumor and normal tissue contours and final plans are reviewed in weekly multidisciplinary SBRT rounds. On the treatment unit, cone beam CT (CBCT) is used for image guidance with therapist manually matching directly to the tumor, adjusting the patient's position for discrepancies >3mm. CBCT is performed for initial localization and repeated during treatment to verify the tumor position. We compared CBCT soft tissue (tumor) matching to bone matching (which would mimic matching used in conventional portal imaging). Patients are followed every 3 months with radiological and clinical assessment. Median pt age was 73 yrs (48-96); mean tumor size was 2.6 cm (range 0.7-5.7). Median follow-up is 10 mo (range 0-26 mo). Acute RT toxicity was generally mild with grade G1 fatigue the most common acute side effect (16 pts). There was 1 episode of G3 dyspnea possibly treatment related, but no other >G2 events. One pt developed G2 RT pneumonitis. 9 pts developed late chest pain at 3-21 mo post SBRT; 4 of those developed rib fractures in the RT field area, 11-21 mo post SBRT. In 38 evaluable pts (40 tumors), 6 CR and 24 PR were observed. There were no local failures in 36 pts with peripheral tumors, but 2 failures in pts treated with the lower 50 Gy/10 fr schedule. CBCT tumor matching compared to bone matching resulted in a mean difference of 6.8mm (±4.9), the difference was >13.9 mm in 10% of pts; this would have resulted in very significant tumor miss if portal imaging was used without proper visualization of the target. These results confirm that lung SBRT gives high rates (95%) of local control with the only local failures observed in the centrally-located tumors treated with lower dose of 50 Gy/10 fr. Acute toxicity is low; rib fracture is the most common late toxicity. CBCT greatly improves the accurate delivery of high radioablative doses of SBRT for early stage lung cancer.

Female patients with soft tissue sarcoma are at a higher risk for developing breast cancer

10071 Background: An increased incidence of MPM has been reported in association with STS. In a series of 1350 adults with STS almost 10% were diagnosed with additional primaries. The incidence of breast cancer (BC) in the general population is 97/105,(Israel-Cancer-Registry) and the incidence of STS is 1.5/105 (Enzinger&amp;Weiss). It is expected that approx. 1.5/105 × 97/105 of the general population will have both BC and STS. Methods: A retrospective search of the database of approx. 1,350 adult STS patients, who were referred, diagnosed, or treated at our center between 1995- 2005. Results: A group of 132 patients (F=62) with STS had at least one additional malignancy. Twenty-five (25/62=40%) had BC, before or after STS. A family history of malignancy was reported by 8/25 patients (32%), 3 with a specific breast cancer family history. STS types varied. Sixteen (16/25) patients had breast cancer as their first primary, 9 as their second or third. Of 17 patients with first primary BC, the sarcoma appeared in the RT field in 2, and in 1 it appeared in a lymphedematous ipsilateral arm. Of eight patients with first primary sarcoma, only one got chemotherapy prior to the diagnosis of BC. Median interval between 1st to 2nd malignancy was 6.9 years (0.7–31y) when the BC was diagnosed first, and 3.8y (0–47y) when the BC was the second. Exposure to carcinogens, or therapeutic radiation and cytotoxics, given for the 1st tumor prior to the 2nd tumor, was recorded in 58%. The incidence of BC among all patients (females + males) with STS-first (in our database) followed by a second malignancy is 8/58 (14%), or 7/23 (30%) female patients with STS-first, or 25/890 (3%) of all female patients with STS in the registry of STS. The incidence of STS among the BC patients is rather low, and most of the cases in this series are not therapy related (14/17). The median survival of patients with BC-first was 312 months, versus 383 months for STS-first (p=NS). Among patients with BC-first, the median survival of patients with RT related sarcoma was 265 months, versus 312 months for RT unrelated STS (p= 0.6). Conclusions: Second primary BC in patients with STS-first is higher than the expected incidence of BC for this population. Screening for BC should be incorporated into the regular follow-up of patients with STS. No significant financial relationships to disclose.

Do pre‐irradiation dental extractions reduce the risk of osteoradionecrosis of the mandible?

This study was done to determine if pre-radiotherapy (pre-RT) dental extractions reduce the risk of osteoradionecrosis (ORN). Between 1987 and 2004, 413 patients with oropharyngeal carcinomas were treated with definitive RT at the University of Florida. Dentate patients underwent pretreatment dental evaluation. Teeth in the RT field were usually extracted if thought to have poor long-term prognosis from dental disease. The endpoint was > or = grade 2 ORN using a modified staging system. Patients were excluded for local recurrence, additional RT above the clavicles, or head and neck surgery besides neck dissection. ORN rates were as follows: edentulous, <1%; teeth in-field with pre-RT extractions, 15%; and teeth in-field without pre-RT extractions, 9%. Patients with poor in-field teeth and pre-RT extractions had a higher 5-year incidence of ORN than those who did not have pre-RT extractions (16% vs 6%, p = .48). Likewise, for those with in-field teeth in good condition and pre-RT extractions, the 5-year ORN incidence was higher than for those who did not undergo extractions (15% vs 2%, p = .42). Multivariate analysis revealed increased ORN risk with doses of >70 Gy, once-daily fractionation, or brachytherapy. Pre-RT extractions do not appear to reduce the risk of ORN.

Impact of patient-specific factors, irradiated left ventricular volume, and treatment set-up errors on the development of myocardial perfusion defects after radiation therapy for left-sided breast cancer

The aim of this study was to assess the impact of patient-specific factors, left ventricle (LV) volume, and treatment set-up errors on the rate of perfusion defects 6 to 60 months post-radiation therapy (RT) in patients receiving tangential RT for left-sided breast cancer. Between 1998 and 2005, a total of 153 patients were enrolled onto an institutional review board-approved prospective study and had pre- and serial post-RT (6-60 months) cardiac perfusion scans to assess for perfusion defects. Of the patients, 108 had normal pre-RT perfusion scans and available follow-up data. The impact of patient-specific factors on the rate of perfusion defects was assessed at various time points using univariate and multivariate analysis. The impact of set-up errors on the rate of perfusion defects was also analyzed using a one-tailed Fisher's Exact test. Consistent with our prior results, the volume of LV in the RT field was the most significant predictor of perfusion defects on both univariate (p = 0.0005 to 0.0058) and multivariate analysis (p = 0.0026 to 0.0029). Body mass index (BMI) was the only significant patient-specific factor on both univariate (p = 0.0005 to 0.022) and multivariate analysis (p = 0.0091 to 0.05). In patients with very small volumes of LV in the planned RT fields, the rate of perfusion defects was significantly higher when the fields set-up "too deep" (83% vs. 30%, p = 0.059). The frequency of deep set-up errors was significantly higher among patients with BMI > or =25 kg/m2 compared with patients of normal weight (47% vs. 28%, p = 0.068). BMI > or =25 kg/m2 may be a significant risk factor for cardiac toxicity after RT for left-sided breast cancer, possibly because of more frequent deep set-up errors resulting in the inclusion of additional heart in the RT fields. Further study is necessary to better understand the impact of patient-specific factors and set-up errors on the development of RT-induced perfusion defects.

71: Dosimetric and Toxicities Comparison Between Prone And Supine Position IMRT For Endometrial Cancer

Intensity-modulated radiotherapy (IMRT) has been shown to reduce the radiation dose to small bowel in pelvic RT in gynecology patients. Prone positioning has also been used to decrease small bowel dose by displacement of small bowel from the RT field in these patients.

Phase I trial of preoperative cetuximab with concurrent continuous infusion 5-fluorouracil and pelvic radiation in patients with local-regionally advanced rectal cancer

3560 Background: Cetuximab, a chimeric anti-EGFR monoclonal antibody, has clinical activity in colorectal cancer with demonstrated safety, efficacy and additive synergy with radiation in solid tumors (head &amp; neck, lung). A pilot trial was therefore designed to investigate the safety of cetuximab in combination with standard neoadjuvant protracted infusion 5-FU and radiation therapy in ultrasound T3–4 (uT3–4) or clinical T4 (cT4) or locally recurrent rectal adenocarcinoma. Secondary objectives of clinical activity were assessed by R0 resection and pathologic complete response (CR) rates. Methods: uT3–4 or cT4 or locally recurrent rectal adenocarcinoma patients received cetuximab 400mg/m2 day 1 (250mg/m2 weekly thereafter) and 5-FU IVCI (225mg/m2) over 5.5 weeks with concurrent pelvic radiation (5040cGy), and cetuximab (250mg/m2 Qweek) for 4 additional weeks, followed by surgical resection 1–3 weeks later. Results: Total Treated: 20 patients (ages 27 - 72), 19 uT3 patients, 1 Local Recurrence patient. Cetuximab Therapy (10 planned treatments): Too early 2 pts, ≥ 8 doses 12 pts, 5 - 8 doses 2 pts, &lt; 5 total doses 4pts* (*cetuximab not given due to: 1 pt - acute cholecystitis from cholelithiasis; 1 pt - Grade 3 radiation perineal toxicity; 2 pts - treatment non-compliance). Radiation Therapy - 18 pts completed, 2 pts too early. Grade 3/4 Toxicities: Diarrhea 10%, Acneiform Rash (outside RT field) 15%, Stomatitis 5%, Radiation Field Dermatitis 5%, Transaminitis 5%. Surgical Outcomes: (17 pts completed surgery): R0 Resection 100%, Pathologic CR 12%. Conclusions: Cetuximab in combination with protracted infusion 5-FU and concurrent radiation is feasible without synergistic or unexpected toxicities. Further randomized investigation of this regimen in the neoadjuvant setting for rectal cancer is warranted. No significant financial relationships to disclose.

Does timing of androgen deprivation influence radiation-induced toxicity? A secondary analysis of Radiation Therapy Oncology Group protocol 9413

4655 Background: We conducted a secondary analysis of RTOG 9413 to compare if the timing of antiandrogen-therapy, concomitant versus adjuvant, influences the incidence of rectal toxicity in whole pelvic radiotherapy. Methods: For the purpose of this secondary analysis, we analyzed the 2 of the 4 arms of the study, in which all patients received radiotherapy to the whole pelvis followed by a boost to the prostate and excluded the two arms that received prostate only radiotherapy. The 2 arms differed only in the timing of the total of 4 months of total androgen deprivation (TAD): arm I (320 patients), TAD was begun 2 months before the start of radiotherapy and continued during radiotherapy. Arm III (319 patients), TAD started immediately after the completion of radiotherapy. Both acute rectal and acute urinary toxicities (CTC v.2.0), testosterone (measured at baseline and yearly after) and other patients data were modeled using the multivariate logistic regression and the multivariate Cox-proportional hazards regression. Results: Median follow up for all patients is 6.0 and 5.8 years (arm I and II, resp.). 43 (13%) patients in each arm had abnormally low testosterone before start of TAD. Late grade 2 - 5 rectal toxicity occurred in 16% and 13% and urinary toxicity in 18% and 20% (arm I and II, resp.). Frequency (or occurrence) of late rectal toxicity (grade 0–1 vs. 2–5, p = 0.2170) and late urinary toxicity (grade 0–1 vs. 2–5, p = 0.4204) are not significantly different between the two arms. The only risk factors for late rectal toxicity in a multivariate regression model was acute rectal toxicity (OR 1.48, p = 0.025), but not abnormal testosterone level at baseline (p = 0.718) or treatment arm (p = 0.874). For late urinary toxicity: age (OR = 1.588, p = 0.010), RT field size (OR 1.004, p &lt; 0.025), baseline testosterone (OR 1.718, p = 0.028), and acute (grade 2–4) toxicity (OR = 1.664, p = 0.006) but not treatment arm (p = 0.928) were risk factors. Conclusions: While late toxicity was not different for concomitant vs. adjuvant hormonal therapy, an abnormally low testosterone level at baseline is a risk factor for late urinary toxicity and not late rectal toxicity. No significant financial relationships to disclose.

SU‐FF‐J‐131: Is There a Relationship Between Body Mass Index, Treatment Set‐Up Errors, and the Development of Myocardial Perfusion Defects Following Radiation Therapy for Left‐Sided Breast Cancer?

Purpose: To assess whether body mass index (BMI) affects the rate of “deep” set‐up errors (i.e. those that increase the volume of heart irradiated), resulting in an increased risk of RT‐induced myocardial perfusion defects (PD) 6–60 months post‐RT. Materials and Methods: For 87 patients receiving RT for left‐sided breast cancer, treatment set‐up accuracy was determined by measuring the height of the lung shadow seen at the level of the central axis on simulation and serial medial tangent portal films. SPECT nuclear medicine scans were performed serially pre‐ and post‐RT to assess for cardiac PD. The interaction among BMI, set‐up error frequency, and the rate of PD was compared using a 1‐tailed Fisher's Exact Test. Results: The rates of deep set‐up deviations were 9/32 vs. 24/51 in patients with BMI&lt;25 kg/m2 and ⩾25 kg/m2, respectively (p=0.068) (Fig 1). When patients were stratified by volume of left ventricle (% LV) in the RT field, set‐up deviations had an impact on the rate of PD in patients with &gt;0% but ⩽1% LV in the field (i.e. patients who are generally predicted to be at very low risk for RT‐induced cardiac dysfunction). The rates of PD in these patients with deep vs. “shallow” set‐up errors (i.e. those that decrease the volume of heart irradiated) were 5/6 vs. 3/10 (p=0.059) (Fig 2). Conclusions: Patients with BMI⩾25 kg/m2 tend to have a higher incidence of deep set‐up errors, causing more heart to be irradiated than intended. In patients with very small volumes of heart in the RT field, those with deep set‐up errors are more likely to have PD post‐RT. Accurate patient set‐up on the treatment machine is critical to minimize the risk of RT‐induced cardiac injury, particularly in overweight and obese patients. Supported by grants 17‐98‐1‐8071 and BC010663 from the DOD.