Heather A. Jones

Concurrent Chemotherapy and Intensity-modulated Radiation Therapy for Anal Carcinoma — Clinical Outcomes in a Large National Cancer Institute-designated Integrated Cancer Centre Network

AIMSnTo report the clinical outcomes of patients with anal carcinoma treated with intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy in a large integrated academic-community cancer centre network.nnnMATERIALS AND METHODSnSeventy-eight patients were treated with IMRT for anal carcinoma at 13 community cancer centres. IMRT planning for all centres was carried out at one central location. Sixty-five patients (83%) were T1-T2, 64% were N0, 9% were M1; five patients were HIV positive. All but one patient received concurrent chemotherapy. The median dose to the pelvis including inguinal nodes was 45 Gy. The primary site and involved nodes were boosted to a median dose of 55.8 Gy. All acute and late toxicities were scored according to the Common Terminology Criteria for Adverse Events, version 3.0.nnnRESULTSnThe median follow-up for the entire cohort was 16 months (range 0-72 months). Acute grade ≥3 toxicity included 27.7% gastrointestinal and 29.0% dermatological. Acute grade 4 haematological toxicity occurred in 12.9% of patients. Sixty-four (88.9%) patients experienced a complete response. The 2 year colostomy-free survival, overall survival, freedom from local failure and freedom from distant failure rates were 81.2, 86.9, 83.6 and 81.8%, respectively.nnnCONCLUSIONSnEarly results seem to confirm that IMRT used concurrently with chemotherapy for treatment of anal carcinoma is effective and well tolerated. This complex treatment can be safely and effectively carried out in a large integrated healthcare network.

Effect of edema associated with 131Cs prostate permanent seed implants on dosimetric quality indices

This study was designed to investigate the effect of prostatic edema on various dosimetric quality indices following transperineal permanent C131s seed implant. Thirty-one patients with early prostate cancer, who received C131s permanent seed implant, were included in this study. Each patient received a prescribed dose of 115 Gy from the implant. Transrectal ultrasound (U.S.) was used to measure the preimplant prostate volume and pre- and postneedle implant volumes, and postimplant CT images were used to obtain postimplant prostate volumes at days 0, 14, and 28 for all patients. The magnitude of edema was determined by comparing the preneedle and postimplant prostate volumes, which was used to compute the half life of the edema using the least-squares method. Dose volume histograms were generated for each set of volumes to determine the percentage of the prostate volume that received a dose equal to or greater than the prescribed dose to compute the quality index (V100) and fractional D90 (FD90). There were no statistically significant differences between the postneedle and postimplant (day 0) volumes obtained by U.S. and CT scanned images (students t-test p=0.56). The mean half life of the edema was found to be (9.72±8.31) days (mean±1SD), ranging from 3.64 to 34.48 days. The mean values of V100 and FD90 from preimplant plan to postimplant plan at day 0 were decreased by 8.0% and 6.3%, respectively. On the other hand, the mean values of V100 and FD90 increased with increasing postimplant time and attained optimal values when postimplant volume reached the original volume of the prostate. The short half life C131s radioactive source delivered about 85% of the prescribed dose before the prostate reached its original volume. Therefore, improvement in V100 and FD90 due to edema decay does not improve the physical dose delivery to the prostate. It is important to note that at the time of C131s implant, the effect of edema must be accounted for when defining the seed positions. Implants performed based only on the guidance of a preimplant volume study would result in poor dosimetric results for C131s implants.

Predictors of Urinary Morbidity in Cs-131 Prostate Brachytherapy Implants

PURPOSEnCesium-131 is a newer radioisotope being used in prostate brachytherapy (PB). This study was conducted to determine the predictors of urinary morbidity with Cs-131 PB.nnnMETHODS AND MATERIALSnA cohort of 159 patients underwent PB with Cs-131 at our institution and were followed by using Expanded Prostate Cancer Index Composite (EPIC) surveys to determine urinary morbidity over time. EPIC scores were obtained preoperatively and postoperatively at 2 and 4 weeks, and 3 and 6 months. Different factors were evaluated to determine their individual effect on urinary morbidity, including patient characteristics, disease characteristics, treatment, and dosimetry. Multivariate analysis of covariance was carried out to identify baseline determinants affecting urinary morbidity. Factors contributing to the need for postoperative catheterization were also studied and reported.nnnRESULTSnAt 2 weeks, patient age, dose to 90% of the organ (D90), bladder neck maximum dose (D(max)), and external beam radiation therapy (EBRT) predicted for worse function. At 4 weeks, age and EBRT continued to predict for worse function. At the 3-month mark, better preoperative urinary function, preoperative alpha blockers, bladder neck D(max), and EBRT predicted for worse urinary morbidity. At 6 months, better preoperative urinary function, preoperative alpha blockers, bladder neck D(max), and EBRT were predictive of increased urinary problems. High bladder neck D(max) and poor preoperative urinary function predicted for the need for catheterization.nnnCONCLUSIONSnThe use of EBRT plus Cs-131 PB predicts for worse urinary toxicity at all time points studied. Patients should be cautioned about this. Age was a consistent predictor of worsened morbidity immediately following Cs-131 PB, while bladder D(max) was the only consistent dosimetric predictor. Paradoxically, patients with better preoperative urinary function had worse urinary morbidity at 3 and 6 months, consistent with recently published literature.

INFLUENCE OF PROSTATIC EDEMA ON 131Cs PERMANENT PROSTATE SEED IMPLANTS: A DOSIMETRIC AND RADIOBIOLOGICAL STUDY

PURPOSEnTo study the influence of prostatic edema on postimplant physical and radiobiological parameters using (131)Cs permanent prostate seed implants.nnnMETHODS AND MATERIALSnThirty-one patients with early prostate cancer who underwent (131)Cs permanent seed implantation were evaluated. Dose-volume histograms were generated for each set of prostate volumes obtained at preimplantation and postimplantion days 0, 14, and 28 to compute quality indices (QIs) and fractional doses at level x (FD(x)). A set of equations for QI, FD(x), and biologically effective doses at dose level D(x) (BED(x)) were defined to account for edema changes with time after implant.nnnRESULTSnThere were statistically significant differences found between QIs of pre- and postimplant plans at day 0, except for the overdose index (ODI). QIs correlated with postimplant time, and FD(x) was found to increase with increasing postimplant time. With the effect of edema, BED at different dose levels showed less improvement due to the short half-life of (131)Cs, which delivers about 85% of the prescribed dose before the prostate reaches its original volume due to dissipation of edema.nnnCONCLUSIONSnResults of the study show that QIs, FD(x), and BEDs at the level of D(x) changed from preneedle plans to postimplant plans and have statistically significant differences (p < 0.05), except for the ODI (p = 0.106), which suggests that at the time of (131)C seed implantation, the effect of edema must be accounted for when defining the seed positions, to avoid the possibility of poor dosimetric and radiobiologic results for (131)Cs seed implants.

Changes in radiobiological parameters in 131 Cs permanent prostate implants.

In prostate permanent implants using Cs seeds, the prostatic edema developed during the implantation procedure, increases the separation between the seeds. This leads to a decrease in the prostate coverage and thus causes an edema induced dose reduction, which results in an increase in tumour cell surviving fraction (SF) with a corresponding decrease in tumour control probability (TCP). To investigate the impact of edema on the SF and the TCP, the expression of the SF of the linear quadratic (LQ) model was extended to account for the effects of edema using the exponential nature of edema resolution and the dose delivered to the edematous prostate. The SF and the TCP for edematous prostate implants were calculated for 31 patients who underwent real time Cs permanent seed implantation. The dose delivered to the edematous prostate was calculated to compute the SF and the TCP for these patients for edema half lives (EHL) ranging from 4 days to 34 days and for edema of magnitudes (M0) varying from 5 to 60% of the actual prostate volume. A reduction in the dose delivered to the edematous prostate was found with the increase of EHL and edema magnitude which results in an increase of the SF, and corresponding decrease in the TCP. The dose reductions in Cs implants varied from 1.1% (for EHL 1⁄4 4 days and M0 1⁄4 5%) to 32.3% (for EHL 1⁄4 34 days and M0 1⁄4 60%). These are higher than the dose reduction in I implants, which vary from 0.3% (for EHL 1⁄4 4 days and M0 1⁄4 5%) to 17.5% (for EHL 1⁄4 34 days and M0 1⁄4 60%). As edema half life increased from 4 days to 34 days and edema magnitude increased from 5 to 60% the SF increased by 4.57 log, and the TCP decreased by 0.80. Compensation of edema induced increase in the SF and decrease in the TCP in Cs seed implants should be carefully done by redefining seed positions with the guidance of post-needle plans. The presented model in this study can be used to estimate the SF or the TCP for pre plan or real time permanent prostate implants using day 0 post-implant CT images.

Edema-induced changes in tumor cell surviving fraction and tumor control probability in 131Cs permanent prostate brachytherapy implant patients

The study is designed to investigate the effect of edema on the delivered dose, tumor cell surviving fraction (SF), and tumor control probability (TCP) in the patients of prostate cancer who underwent u2009131Cs permanent seed implantation. The dose reduction, the SF, and the TCP for edematous prostate implants were calculated for 31 patients who underwent real‐time u2009131Cs permanent seed implantation for edema half‐lives (EHL), ranging from 4 days to 34 days and for edema magnitudes (M0) varying from 5% to 60% of the actual prostate volume. A dose reduction in u2009131Cs implants varied from 1.1% (for EHL=4u2009days and M0=5%) to 32.3% (for EHL=34u2009days and M0=60%). These are higher than the dose reduction in u2009125I implants, which vary from 0.3% (for EHL=4u2009days and M0=5%) to 17.5% (for EHL=34u2009days and M0=60%). As EHL increased from 4 days to 34 days and edema magnitude increased from 5% to 60%, the natural logarithmic value of SF increased by 4.57 and the TCP decreased by 0.80. Edema induced increase in the SF and decrease in the TCP in u2009131Cs seed implants, is significantly more pronounced in a combination of higher edema magnitude and larger edema half‐lives than for less edema magnitude and lower edema half‐lives, as compared for M0=60% and EHL=34, and M0=5% and EHL=4u2009days. PACS number: 87.53.Jw

SU‐GG‐T‐91: Effect of Edema on Survival Fraction and Biologically Effective Dose in 131Cs Prostate Permanent Seed Implants

Purpose: To investigate the effect of edema on Survival Fraction(SF), and Biologically Effective Dose(BED) in 131Cs prostate permanent seed implants. Materials and Methods: To account the effect of edema decay on SF and BED with post implant time, the following relations were derived S ( D ) = 1 V ∑ i =1 n [{ V pi + Δ V i exp (−λ e t )}S i (D)] and BED = −(1/α) ln [ S ( D )] Where V, Vpi, ΔVi, λe and t are the initial tumor volume with edema, pre‐edema volume of ith voxel, amount of edema at day 0 in ith voxel, edema decay constant and post implant time, respectively. S i (D) is the SF of cells in ith voxel with dose protraction factor which consists decay constant of radioactive source and repair constant of sublethal damage. Dose volume histograms(DVH) of 31 patients with prostate cancer, who underwent 131Cs implantations, were used to computeS(D) and BED using values of LQ model parameters given in the AAPM TG‐137 report, and edema decay constant λe=0.0713d−1. Results: S(D) and BED values, obtained for reference dose without edema correction, with edema decay to CTimages at 0 day and individual CTimages at 14 and 28 days, are 9.45×10−6 and 77.13Gy, 1.52×10−5±3.92×l0−5 and 74.05±4.99Gy, and 1.048×10−5±4.96×10−6 and 80.33±4.20Gy at day 14, and 1.57×10−7 and 104.46Gy, 1.31×10−6 ±5.24×10−6 and 90.35±6.38Gy, and 1.082×10−6±8.023×10−7 and 99.96±6.69Gy at day 28, respectively. There is statistically significant differences between the reference values and edema corrected values(p 0.05) were found. Conclusions: The described equations with an account of edema decay provides accurate values of S(D) and BED at different post implant times. It can be concluded that the effect of edema must be accounted at the time of implant, and implants should not be performed based on pre‐implant volume study in 131Cs implants.

SU-FF-T-44: Dosimetric Analysis of the Effect of Edema in 131Cs Prostate Permanent Seed Implants

Purpose: To investigate the effect of edema on different dosimetric parameters in 131 Cs prostate permanent seed implants. Materials and Methods: Transrectal ultrasound(US) and computertomography(CT)images were used to determine pre‐ and post‐needle implant volumes, and post‐implant prostate volumes in 31 patients who had received 131 Cs implant. Dose volume histograms(DVH) were generated to determine the prostate volumes that received 100%, 150% and 200% of prescribed dose to calculate quality indices(QIs) and fractional D90(FD90) for each set of volumes for all patients. Results: No statistical differences were found between post‐needle and post‐implant(day 0) volumes obtained by US and CTimages(p=0.56). The half life of the edema was found to be 9.72days. The change in mean values of coverage index(CI), dose non‐uniformity ratio(DNR), overdose index(ODI), relative dose‐homogeneity index(DHI) and FD90 can be described by CI ( t )= CI (0)+[1− CI (0)][1− exp (−λ CI t )] (1) DNR ( t )= DNR (0)+[1− DNR (0)][1− exp (−λ DNR t )] (2) ODI ( t )= ODI (0)+[1− ODI (0)][1− exp (−λ ODI t )] (3) DHI ( t )= DHI (0) exp (−λ DHI t ) (4) and D 90( t )=( R 0 /λ) exp (−λ t ){ FD 90(0)+[ FD 90(0)− a ][1− exp (−λ FD t )]} (5) differential equations. The values of correlation coefficients and time constants obtained from least square fit of these equations were found to be 0.9867 & 0.0316 for CI, 0.9988 & 0.0148 for DNR, 0.9958 & 0.00148 for ODI, and 0.9983 & 0.0125 for DHI, respectively. Conclusions: CI, DHI and FD90 decreased, while DNR and ODI increased from pre‐implant plans to post‐implant plans at day 0 due to edema formation. CI, DNR, ODI and FD90 increased and DHI decreased with increasing post‐implant time and attained optimal values in 4 weeks. During this period 85% dose is delivered due to short half life of 131 Cs seeds. Therefore, it is important to account for the effect of edema at the time of implant while defining seed positions. Implants performed based on pre‐implant volume study only result in poor dosimetric results in 131 Cs implants.