Yasmin Hasan

Clinical Outcomes of Intensity-Modulated Pelvic Radiation Therapy for Carcinoma of the Cervix

PURPOSE To evaluate disease outcomes and toxicity in cervical cancer patients treated with pelvic intensity-modulated radiation therapy (IMRT). METHODS AND MATERIALS We included all patients with Stage I-IVA cervical carcinoma treated with IMRT at three different institutions from 2000-2007. Patients treated with extended field or conventional techniques were excluded. Intensity-modulated radiation therapy plans were designed to deliver 45 Gy in 1.8-Gy daily fractions to the planning target volume while minimizing dose to the bowel, bladder, and rectum. Toxicity was graded according to the Radiation Therapy Oncology Group system. Overall survival and disease-free survival were estimated by use of the Kaplan-Meier method. Pelvic failure, distant failure, and late toxicity were estimated by use of cumulative incidence functions. RESULTS The study included 111 patients. Of these, 22 were treated with postoperative IMRT, 8 with IMRT followed by intracavitary brachytherapy and adjuvant hysterectomy, and 81 with IMRT followed by planned intracavitary brachytherapy. Of the patients, 63 had Stage I-IIA disease and 48 had Stage IIB-IVA disease. The median follow-up time was 27 months. The 3-year overall survival rate and the disease-free survival rate were 78% (95% confidence interval [CI], 68-88%) and 69% (95% CI, 59-81%), respectively. The 3-year pelvic failure rate and the distant failure rate were 14% (95% CI, 6-22%) and 17% (95% CI, 8-25%), respectively. Estimates of acute and late Grade 3 toxicity or higher were 2% (95% CI, 0-7%) and 7% (95% CI, 2-13%), respectively. CONCLUSIONS Intensity-modulated radiation therapy is associated with low toxicity and favorable outcomes, supporting its safety and efficacy for cervical cancer. Prospective clinical trials are needed to evaluate the comparative efficacy of IMRT vs. conventional techniques.

The effect of treatment time in locally advanced cervical cancer in the era of concurrent chemoradiotherapy.

This study sought to determine if treatment time impacts pelvic failure (PF), distant failure (DF), or disease‐specific mortality (DSM) in patients undergoing concurrent chemoradiotherapy (CCRT).

Image Guidance in External Beam Accelerated Partial Breast Irradiation: Comparison of Surrogates for the Lumpectomy Cavity

PURPOSE To compare localization of the lumpectomy cavity by using breast surface matching vs. clips for image-guided external beam accelerated partial breast irradiation. METHODS AND MATERIALS Twenty-seven patients with breast cancer with two computed tomography (CT) scans each had three CT registrations performed: (1) to bony anatomy, (2) to the center of mass (COM) of surgical clips, and (3) to the breast surface. The cavity COM was defined in both the initial and second CT scans after each type of registration, and distances between COMs (DeltaCOM(Bone), DeltaCOM(Clips), and DeltaCOM(Surface)) were determined. Smaller DeltaCOMs were interpreted as better localizations. Correlation coefficients were calculated for DeltaCOM vs. several variables. RESULTS The DeltaCOM(Bone) (mean, 7 +/- 2 [SD] mm) increased with breast volume (r = 0.4; p = 0.02) and distance from the chest wall (r = 0.5; p = 0.003). Relative to bony registration, clip registration provided better localization (DeltaCOM(Clips) < DeltaCOM(Bone)) in 25 of 27 cases. Breast surface matching improved cavity localization (DeltaCOM(Surface) < DeltaCOM(Bone)) in 19 of 27 cases. Mean improvements (DeltaCOM(Bone) - DeltaCOM(Clips or Surface)) were 4 +/- 3 and 2 +/- 4 mm, respectively. In terms of percentage of improvement ([DeltaCOM(Bone) - DeltaCOM(Clips or Surface)]/DeltaCOM(Bone)), only surface matching showed a correlation with breast volume. Clip localization outperformed surface registration for cavities located superior to the breast COM. CONCLUSIONS Use of either breast surface or surgical clips as surrogates for the cavity results in improved localization in most patients compared with bony registration and may allow smaller planning target volume margins for external beam accelerated partial breast irradiation. Compared with surface registration, clip registration may be less sensitive to anatomic characteristics and therefore more broadly applicable.

Comparison of Planned Versus Actual Dose Delivered for External Beam Accelerated Partial Breast Irradiation Using Cone-Beam CT and Deformable Registration

PURPOSE To assess the adequacy of dose delivery to the clinical target volume (CTV) using external beam (EB) accelerated partial breast irradiation (APBI). METHODS AND MATERIALS Sixteen patients treated with EB APBI underwent cone beam CT (CBCT) before each fraction and daily helical CT (HCT) scans to determine setup errors and calculate the dose per fraction. For 12 patients, an in-house image-intensity-based deformable registration program was used to register the HCTs to the planning CT and generate the cumulative dose. Treatment was 38.5 Gy in 10 fractions. EB APBI constraints from the National Surgical Adjuvant Breast and Bowel Project B39/Radiation Therapy Oncology Group 0413 Phase III protocol were used. RESULTS The mean setup error per CBCT registration was 9 ± 5 mm. Dose-volume histogram analysis showed only one patient (8%) with a decrease in the CTV V90 (8% underdosage). All other patients demonstrated adequate target coverage. PTV_EVAL V90 was on average 3% (range, 0%-16%) less than planned. For the ipsilateral breast, four patients had an increase in V50 (≤ 1% increase) and three patients had an increase in V100 (≤ 9% increase). Only one patient showed an increase >5%. Four patients had an increase in ipsilateral lung V30 (maximum 3%), and one had an increase in heart V5 (1%). Four patients had an increase in MaxDose (maximum 89 cGy). CONCLUSIONS The current CTV-to-PTV margin of 10 mm appears sufficient for ∼92% of patients treated with EB APBI. Although expansion of the population PTV margin to 14 mm would provide ∼97% confidence level for CTV coverage, online image guidance should be considered.

A Prospective Study of the Utility of Magnetic Resonance Imaging in Determining Candidacy for Partial Breast Irradiation

PURPOSE Retrospective data have demonstrated that breast magnetic resonance imaging (MRI) may change a patients eligibility for partial breast irradiation (PBI) by identifying multicentric, multifocal, or contralateral disease. The objective of the current study was to prospectively determine the frequency with which MRI identifies occult disease and to establish clinical factors associated with a higher likelihood of MRI prompting changes in PBI eligibility. METHODS AND MATERIALS At The University of Chicago, women with breast cancer uniformly undergo MRI in addition to mammography and ultrasonography. From June 2009 through May 2011, all patients were screened prospectively in a multidisciplinary conference for PBI eligibility based on standard imaging, and the impact of MRI on PBI eligibility according to National Surgical Adjuvant Breast and Bowel Project protocol B-39/Radiation Therapy Oncology Group protocol 0413 entry criteria was recorded. Univariable analysis was performed using clinical characteristics in both the prospective cohort and in a separate cohort of retrospectively identified patients. Pooled analysis was used to derive a scoring index predictive of the risk that MRI would identify additional disease. RESULTS A total of 521 patients were screened for PBI eligibility, and 124 (23.8%) patients were deemed eligible for PBI based on standard imaging. MRI findings changed PBI eligibility in 12.9% of patients. In the pooled univariable analysis, tumor size ≥ 2 cm on mammography or ultrasonography (P=.02), age <50 years (P=.01), invasive lobular histology (P=.01), and HER-2/neu amplification (P=.01) were associated with a higher likelihood of MRI changing PBI eligibility. A predictive score was generated by summing the number of significant risk factors. Patients with a score of 0, 1, 2, and 3 had changes to eligibility based on MRI findings in 2.8%, 13.2%, 38.1%, and 100%, respectively (P<.0001). CONCLUSIONS MRI identified additional disease in a significant number of patients eligible for PBI, based on standard imaging. Clinical characteristics may be useful in directing implementation of MRI in the staging of PBI candidates.

Hypofractionated radiotherapy does not increase acute toxicity in large-breasted women: results from a prospectively collected series.

Background and Purpose:To compare the acute toxicity of hypofractionated whole breast radiotherapy (HypoRT) to conventionally fractionated radiotherapy (ConvRT) in large-breasted women with early stage disease. Materials and Methods:Women with breast volume>1500 cm3, body mass index>30 kg/m2, or separation>25 cm treated with HypoRT or ConvRT from 2005 through 2010 were identified from a prospective database and included in the analysis. Acute toxicity was scored for each treated breast. Results:Ninety-two patients were treated to 96 breasts. The median body mass index was 33 kg/m2 and median breast volume was 1932 cm3 for the ConvRT group compared with 32.4 kg/m2 and 1825 cm3 for the HypoRT group. Maximum acute skin toxicity consisted of focal moist desquamation in 26% and 11% of the ConvRT and HypoRT patients, respectively (P=0.002). Breast volume was the only patient factor significantly associated with moist desquamation on multivariable analysis (P=0.01). Among those with a breast volume >2500 cm3, focal moist desquamation occurred in 40.7% (11/27) compared with 11.1% (7/63) in patients with breast volume <2500 cm3 (P=0.002). Conclusions:Among obese and large-breasted women, there was no increase in acute skin toxicity with the use of HypoRT. HypoRT should be considered in obese and large-breasted women when advanced planning techniques are used.

Assessment of interfractional variation of the breast surface following conventional patient positioning for whole-breast radiotherapy

The purpose of this study was to quantify the variability of the breast surface position when aligning whole‐breast patients to bony landmarks based on MV portal films or skin marks alone. Surface imaging was used to assess the breast surface position of 11 whole‐breast radiotherapy patients, but was not used for patient positioning. On filmed fractions, AlignRT v5.0 was used to capture the patients surface after initial positioning based on skin marks (28 “preshifts” surfaces), and after treatment couch shifts based on MV films (41 “postshifts” surfaces). Translations and rotations based on surface captures were recorded, as well as couch shifts based on MV films. For nonfilmed treatments, “daily” surface images were captured following positioning to skin marks alone. Group mean and systematic and random errors were calculated for all datasets. Pearson correlation coefficients, setup margins, and 95% limits of agreement (LOA) were calculated for preshifts translations and MV film shifts. LOA between postshifts surfaces and the filmed treatment positions were also computed. All the surface captures collected were retrospectively compared to both a DICOM reference surface created from the planning CT and to an AlignRT reference surface. All statistical analyses were performed using the DICOM reference surface dataset. AlignRT reference surface data was only used to calculate the LOA with the DICOM reference data. This helped assess any outcome differences between both reference surfaces. Setup margins for preshifts surfaces and MV films range between 8.3–12.0 mm and 5.4–13.4 mm, respectively. The largest margin is along the left–right (LR) direction for preshift surfaces, and along craniocaudal (CC) for films. LOA ranges between the preshifts surfaces and MV film shifts are large (12.6–21.9 mm); these decrease for postshifts surfaces (9.8–18.4 mm), but still show significant disagreements between the two modalities due to their focus on different anatomical landmarks (patients topography versus bony anatomy). Pearsons correlation coefficients further support this by showing low to moderate correlations in the anterior–posterior (AP) and LR directions (0.47–0.69) and no correlation along CC(<0.15). The use of an AlignRT reference surface compared to the DICOM reference surface does not significantly affect the LOA. Alignment of breast patients based solely on bony alignment may lead to interfractional inconsistencies in the breast surface position. The use of surface imaging tools highlights these discrepancies, and allows the radiation oncology team to better assess the possible effects on treatment quality. PACS number: 87

Outcomes for patients with cervical cancer treated with extended-field intensity-modulated radiation therapy and concurrent cisplatin.

Objective To evaluate disease outcomes and toxicity in patients with cervical cancer treated with extended-field intensity-modulated radiotherapy. Materials and Methods We included all patients treated with extended-field intensity-modulated radiotherapy and concurrent weekly cisplatin from 2003 to 2010 at 2 institutions. Overall survival and disease-free survival were estimated using Kaplan-Meier method. Locoregional failure (LRF), distant failure, and competing mortality were calculated using cumulative incidence functions. Acute and late toxicity were graded using Common Terminology Criteria for Adverse Events (CTCAE) and Radiation Therapy Oncology Group late radiation morbidity scoring criteria, respectively. Results The study included 21 patients, 14 and 20 of which had positive para-aortic and pelvic nodes, respectively. The median follow-up was 22 months. Eighteen-month overall survival and disease-free survival were 59.7% (95% confidence interval [CI], 41.2%–86.4%) and 42.9% (95% CI, 26.2%–70.2%). Eighteen-month cumulative incidences of LRF, distant failure, and competing mortality were 9.5% (95% CI, 1.5–26.8%), 42.9% (95% CI, 21.3–62.9%), and 4.8% (95% CI, 0.3–20.2%), respectively. Eighteen-month cumulative incidences of late grade 3 or higher-grade genitourinary and gastrointestinal toxicity were 4.8% (95% CI, 0.2%–20.3%) and 0%, respectively. Conclusions Intensity-modulated extended-field radiotherapy was associated with low rates of late toxicity and LRF. High rates of distant failure indicate that this group of patients could benefit from intensified systemic therapy.

Longitudinal study of acute haematologic toxicity in cervical cancer patients treated with chemoradiotherapy.

Acute hematologic toxicity (HT) limits optimal delivery of concurrent chemoradiotherapy (CRT) for patients with pelvic malignancies. We tested the hypothesis that pelvic bone marrow (PBM) dose‐volume metrics were associated with weekly reductions in peripheral blood cell counts in cervical cancer patients undergoing CRT.

Effect of RTOG breast/chest wall guidelines on dose-volume histogram parameters*

Treatment planning for breast cancer has been traditionally based on clinical landmarks. The Radiation Therapy Oncology Group (RTOG) published consensus guidelines on contouring target volumes (TV) for the breast/chest wall and draining lymphatics. The effect of these guidelines on dosimetric parameters in surrounding organs at risk (OAR) and TVs is unknown. Fourteen patients treated with clinically derived plans from 2007‐2011 (Group I) and fourteen patients treated with target volume‐based plans from 2011‐2012 were selected for comparison (Group II). Treatment plans were constructed based on clinical landmarks (Group I) or TVs (Group II) to a median dose of 50.4 Gy to the breast/chest wall, axilla (Ax), supraclavicular (SCV), and internal mammary (IMN) lymph nodes. The RTOG TVs were then contoured in Group I patients by a single investigator blinded to the dose distributions. Dose‐volume histograms (DVH) were computed for the RTOG TVs and OARs in both groups, and DVH parameters were compared. In Group II, coverage improved for the SCV (V90=78.0% versus 93.6%, p=0.02) and intact breast (V95=95.6% versus 99.3%, p=0.007). The dose to the cord, the lung (V20Gy and V30Gy), and contralateral breast (V5Gy) were the same. Finally, the low dose to the heart and lung was decreased in Group II (heart V5Gy=48.7% versus 27.3%, p=0.02, heart V10Gy=33.5% vs. 17.5%, p=0.01, and ipsilateral lung V5Gy=84.5% vs. 69.3%, p=0.001). Overall, our study supports that treatment planning using the RTOG consensus guidelines can improve coverage to certain target volumes compared to treatments based solely on clinical landmarks. Additionally, treatment planning using these target volumes does not increase dose to the contralateral breast, cord, heart, or lungs. Longer follow‐up is needed to determine if using these target volumes will affect clinical outcomes. PACS number: 87.55.dk