John Pedersen

A treatment planning study comparing helical tomotherapy with intensity-modulated radiotherapy for the treatment of anal cancer

PURPOSE A planning study to compare helical tomotherapy (HT) and intensity-modulated radiotherapy (IMRT) for the treatment of anal canal cancer. MATERIALS AND METHODS Sixteen (8 males and 8 females) patients with anal cancer previously treated radically were identified. HT and IMRT plans were generated and dosimetric comparisons of the plans were performed. The planning goals were to deliver 54Gy to the tumor (PTV(54Gy)) and 48Gy to the nodes at risk (PTV(Node)) in 30 fractions. RESULTS PTVs: HT plans were more homogeneous for both men and women. Male patients: HT vs. IMRT: D(max): 55.87+/-0.58 vs. 59.17+/-3.24 (p=0.036); D(min): 52.91+/-0.36 vs. 44.09+/-6.84 (p=0.012); female patients: HT vs. IMRT: D(max): 56.14+/-0.71 vs. 59.47+/-0.81 (p=0.012); D(min): 52.36+/-0.87 vs. 50.97+/-1.42 (p=0.028). OARs: In general, HT plans delivered a lower dose to the peritoneal cavity, external genitalia and the bladder and IMRT plans resulted in greater sparing of the pelvic bones (iliac crest/femur) for both men and women. Iliac crest/femur: the difference was significant only for the mean V10Gy of iliac crest in women (p< or =0.012). External genitalia: HT plans achieved better sparing in women compared to men (p< or =0.046). For men, the mean doses were 18.96+/-3.17 and 15.72+/-3.21 for the HT and IMRT plan, respectively (p< or =0.017). Skin: both techniques achieved comparable sparing of the non-target skin (p=NS). CONCLUSIONS HT and IMRT techniques achieved comparable target dose coverage and organ sparing, whereas HT plans were more homogeneous for both men and women.

Time course of prostatic edema post permanent seed implant determined by magnetic resonance imaging

PURPOSE To quantify the time course of postimplant prostatic edema magnitude and spatial isotropy using serial magnetic resonance imaging (MRI). METHODS AND MATERIALS Forty patients with histologic diagnosis of prostate cancer received an iodine-125 seed implant (Day 0) and consented to 1.5-T MRI on Days -1, 0, 14, and 28. Seeds of strength 0.39mCi were placed in a modified peripheral loading pattern to deliver 145Gy to the target volume. MR images consisted of 3-4mm thick axial slices with no gap. The image sets were anonymized and randomized to minimize contouring bias, then contoured by a single radiation oncologist. Contours were reoriented about their center of mass to align the prostate long axis with the superior-inferior (S-I) direction; prostate volumes and dimensions in the left-right (L-R), anterior-posterior (A-P), and S-I directions through the center of mass were calculated. RESULTS The average relative edema volume was 1.18±0.14 (1standard deviation) on Day 0 and 1.01±0.15 on Day 30. Between Days 0 and 30, the edema resolved linearly with time on average. Average relative edema dimensions on Day 0 in the L-R, A-P, and S-I directions were 1.01±0.07, 1.11±0.09, and 1.08±0.13, respectively. CONCLUSIONS As measured using MRI, the average edema magnitude for our study population was ∼20% on Day 0 and resolved linearly with time to ∼0% on Day 30. The edema exhibited spatial anisotropy, the prostate expanding on Day 0 by ∼10% in each of the A-P and S-I directions and by ∼0% in the L-R direction.

Can Images Obtained With High Field Strength Magnetic Resonance Imaging Reduce Contouring Variability of the Prostate

PURPOSE The objective of this study is to determine whether there is less contouring variability of the prostate using higher-strength magnetic resonance images (MRI) compared with standard MRI and computed tomography (CT). METHODS AND MATERIALS Forty patients treated with prostate brachytherapy were accrued to a prospective study that included the acquisition of 1.5-T MR and CT images at specified time points. A subset of 10 patients had additional 3.0-T MR images acquired at the same time as their 1.5-T MR scans. Images from each of these patients were contoured by 5 radiation oncologists, with a random subset of patients repeated to quantify intraobserver contouring variability. To minimize bias in contouring the prostate, the image sets were placed in folders in a random order with all identifiers removed from the images. RESULTS Although there was less interobserver contouring variability in the overall prostate volumes in 1.5-T MRI compared with 3.0-T MRI (p < 0.01), there was no significant differences in contouring variability in the different regions of the prostate between 1.5-T MRI and 3.0-T MRI. MRI demonstrated significantly less interobserver contouring variability in both 1.5-T and 3.0-T compared with CT in overall prostate volumes (p < 0.01, p = 0.01), with the greatest benefits being appreciated in the base of the prostate. Overall, there was less intraobserver contouring variability than interobserver contouring variability for all of the measurements analyzed. CONCLUSIONS Use of 3.0-T MRI does not demonstrate a significant improvement in contouring variability compared with 1.5-T MRI, although both magnetic strengths demonstrated less contouring variability compared with CT.

Comparison of prostate volume, shape, and contouring variability determined from preimplant magnetic resonance and transrectal ultrasound images.

PURPOSE To compare preimplant prostate contours and contouring variability between magnetic resonance (MR) and transrectal ultrasound images. METHODS AND MATERIALS Twenty-three patients were imaged using ultrasound (US) and MR before permanent brachytherapy treatment. Images were anonymized, randomized, and duplicated, and the prostate was independently delineated by five radiation oncologists. Contours were compared in terms of volume, dimensions, posterior rectal indentation, and observer variability. The Jaccard index quantified spatial overlap between contours from duplicated images. RESULTS The mean US/MR volume ratio was 0.99±0.08 (p=0.5). The width, height, and length ratios for the prostate were 0.98±0.06 (p=0.09), 0.99±0.08 (p=0.4), and 1.05±0.14 (p=0.1). Rectal indentation was larger on US by 0.18mL (p=0.01) and correlated with prostate volume (p<0.01). MR and US interobserver variability in volume were similar at 3.5±1.7 and 3.3±1.9mL (p=0.6). Intraobserver variability was smaller on US at 1.4±1.1mL compared with MR at 2.4±2.2mL (p=0.01). Local intraobserver variability was lower on US at the midgland slice (p<0.01) but lower on MR at the base (p<0.01) and apex (p<0.01) slices. CONCLUSIONS US is comparable to MR for preimplant prostate delineation, with no significant difference in volume and dimensions. Rectal indentation because of the transrectal ultrasound probe was measurable, although the effects were small. Intraobserver variability was lower on US for the prostate volume but was lower on MR locally at the base and apex. However, the difference was not observed for the interobserver variability, which was similar between MR and US.

Analysis of early and late deaths on RTOG non-small cell carcinoma of the lung trials: comparison with CALGB 8433☆

UNLABELLED In a major study that showed a treatment advantage for induction chemotherapy followed by radiation therapy (CALGB 8433), there was a significantly (P = 0.02) lower proportion of patients dying within 105 days of registration in the chemotherapy/radiation arm than the radiation therapy arm; without this difference, the overall survival was marginally better (P = 0.059) for the chemotherapy/radiation group. A retrospective analysis of RTOG trials sought explanations for the phenomenon. MATERIALS AND METHODS Patients who fit the CALGB eligibility criteria and received radiation therapy alone in four prospective trials of the RTOG conducted between 1983 and 1989 were analyzed to determine factors that distinguished patients dying within 105 days from longer survivors. Two were trials of altered fractionation and two used standard fractionation. Of 683 patients identified, 107 (15.7%) died within 105 days after registration. The log linear model was used to evaluate relationships between death within 105 days and known prognostic factors. Karnofsky performance status (KPS), < 90 vs. > or = 90, was the only factor significantly related to death within 105 days (P = 0.0052). A Cox model with the same factors plus fractionation and total dose found KPS and T-stage associated with overall survival (P = 0.0005 and 0.025, respectively). The choice of the hyperfractionation arm (HFX) for Phase III study (69.6 Gy at 1.2 Gy b.i.d.) was based in part on comparison with standard fractionation (STD) from a concurrent RTOG protocol, 8321. Review of early deaths showed that this HFX arm had a lower proportion of patients dying within 105 days (7.9%) than STD in 8321 (21.0%).(ABSTRACT TRUNCATED AT 250 WORDS)

Radiation and concurrent chemotherapy for the treatment of Lewis lung tumor and B16 melanoma tumor in C57/BL mice☆

C57/BL mice bearing either Lewis lung tumor or B16 melanoma tumor were treated with radiation and concurrent chemotherapy. The treatment results were determined in vivo by tumor regrowth delay assay. When continuous infusion of either Cyclophosphamide (CYCLO) or 5-Fluorouracil (5-FU) or Adriamycin (ADRIA) or Mitomycin-C (MITO-C) was used in combination with continuous radiation at 1 cGy/min, no increase in tumor regrowth delay was observed over that of radiation alone. When multiple drug chemotherapy, FAM (5-FU, ADRIA, MITO-C) was administered in combination with radiation at 80 cGy/min, no increase in tumor regrowth delay was observed over that of radiation alone. In these two murine tumor models, when clinically relevant concentrations of commonly used chemotherapy agents were combined with radiation, no therapeutic advantage was observed.

Distinguishing prostate-specific antigen bounces from biochemical failure after low-dose-rate prostate brachytherapy.

Purpose The purpose of this study was to characterize benign prostate-specific antigen (PSA) bounces of at least 2.0 ng/mL and biochemical failure as defined by the Phoenix definition after prostate brachytherapy at our institution, and to investigate distinguishing features between three outcome groups: patients experiencing a benign PSA bounce, biochemical failure, or neither. Material and methods Five hundred and thirty consecutive men treated with low-dose-rate brachytherapy with follow-up of at least 3 years were divided into outcome groups experiencing bounce, failure, or neither. A benign bounce was defined as a rise of at least 2.0 ng/mL over the pre-rise nadir followed by a decline to 0.5 ng/mL or below, without intervention. Patient and tumor characteristics, treatment variables, and PSA kinetics were analyzed between groups. Results Thirty-two (6.0%) men experienced benign bounces and 47 (8.9%) men experienced failure. Men experiencing a bounce were younger (p = 0.01), had a higher 6-month PSA level (p = 0.03), and took longer to reach a final nadir (p < 0.01). Compared to the failure group, men with bounce had a lower pre-treatment PSA level (p = 0.01) and experienced a rise of at least 2.0 ng/mL that occurred sooner after the implant (p < 0.01) with a faster PSA doubling time (p = 0.01). Only time to PSA rise independently differentiated between bounce and failure (p < 0.01), with a benign bounce not being seen after 36 months post-treatment. Prostate-specific antigen levels during a bounce reached levels as high as 12.6 ng/mL in this cohort, and in some cases took over 5 years to decline to below 0.5 ng/mL. Conclusions Although there is substantial overlap between the features of benign PSA bounces and failure, physicians may find it useful to evaluate the timing, absolute PSA level, initial response to treatment, and rate of rise when contemplating management for a PSA rise after low-dose-rate brachytherapy.

Comparison of low and intermediate source strengths for 125I prostate brachytherapy implants

PURPOSE To compare the implant quality and clinical outcomes for patients treated with low and intermediate strength (125)I seeds in prostate brachytherapy implants. METHODS AND MATERIALS This retrospective review included 390 consecutive patients treated with prostate brachytherapy from 1999 to 2006. The first 142 patients were implanted with source strengths lower than 0.415U (0.327mCi), with the subsequent 248 patients implanted with source strengths higher than 0.493U (0.388mCi). Clinical, dosimetric, toxicity, and outcome data were compared between these two cohorts of patients. RESULTS Despite having similar prostate volumes, fewer sources (median, 95 vs. 113; p<0.0001) and fewer needles (median, 23 vs. 29; p<0.0001) were implanted in the intermediate strength cohort. The postimplant dosimetry demonstrated better quality implants in patients treated with intermediate strength sources (median D90, 160.0Gy vs. 139.6Gy; p<0.0001), with greater dose inhomogeneity identified in the intermediate strength cohort of patients. A higher incidence of late rectal toxicity was identified in patients treated with intermediate strength sources despite lower rectal doses in this cohort. The biochemical relapse-free survival, prostate cancer survival, and overall survival were not significantly different between the two cohorts. CONCLUSIONS The transition from low to intermediate strength sources has led to fewer resources being used and improved postoperative dosimetry. Although there were more rectal complications identified in the intermediate strength cohort of patients in this analysis, there were no other significantly worse clinical or biochemical outcomes for patients implanted with intermediate strength sources.

Azomycin riboside: A new radiosensitizer☆☆☆

Azomycin riboside (2-nitro-1-beta-D-ribofuranosylimidazole) (AR), a nucleoside analogue with the base component replaced by a 2-nitroimidazole was studied to determine its potential as a radiosensitizer. In vitro evidence showed that AR is as good as or slightly better than misonidazole (MISO) as a hypoxic cell radiosensitizer. AR was also found to kill hypoxic cells directly and this cytotoxicity was at least as great as MISO cytotoxicity. However, when tumor regrowth delay was used to assess in vivo radiosensitization, AR was found to be inferior to MISO while the LD50 host toxicity assay indicated that AR might be nearly as toxic as MISO. Unless AR proves to be less toxic than MISO or can be selectively distributed with nucleoside transport inhibitors, these preliminary observations have not shown any advantage of AR over MISO as a potential clinically useful radiosensitizer.

Cytotoxic and radiosensitizing effects of misonidazole on hematopoiesis in normal and tumor-bearing mice

Abstract Misonidazole is a 2-nitroimidazole hypoxic cell radiosensitizing agent currently undergoing clinical trials. Preliminary studies have shown that misonidazole is toxic to human hematopoietic stem cells. A survey of the effects of misonidazole on a variety of murine hematopoietic stem cells was undertaken. No cytotoxicity or radiosensitization could be demonstrated when misonidazole was administered in vivo , in assays of transplantable spleen colony cells (CFU-S), endogenous spleen colony cells and committed granulocyte-macrophage precursors (CFU-C). The ability of misonidazole to radiosensitize hypoxic CFU-S was confirmed. Misonidazole was toxic to bone marrow when incubated in vitro in liquid cultures for long periods at higher concentrations than that attainable in vivo . CFU-C proliferation was also assessed in animals bearing Lewis lung tumor. No toxicity could be demonstrated when there was a marked increase in CFU-C activity following tumor implantation or when the tumors had grown large enough to have a significant hypoxic portion. These studies indicate that misonidazole is not toxic to murine hematopoiesis in vivo , but there are indications that it may be toxic in situations in which relatively high concentrations are maintained for long periods of time.