Daniel E. Soto

Correlation between pretreatment FDG-PET biological target volume and anatomical location of failure after radiation therapy for head and neck cancers.

BACKGROUND AND PURPOSE To assess whether the pretreatment FDG-PET-defined biologic target volume (PET-BTV) correlates with the anatomical sites of loco-regional failure (LRF) after RT for head and neck cancer (HNC). MATERIALS AND METHODS We retrospectively identified 61 HNC patients treated definitively with either 3-D CRT or IMRT who had a pre-therapy PET/CT. The GTV and high-risk CTV(1) definitions included composite data obtained from diagnostic CT, PET/CT, physical examination, and MRI when available. The median CTV(1) dose was 70Gy. 95% received chemotherapy. For patients with LRF, a recurrence volume (V(r)) was identified and was mapped to the pretreatment planning CT and pretreatment PET scan. RESULTS At a median follow-up of 22 months, 15% (9/61) patients had LRF. For patients with a LRF, 100% (9/9) of failures were inside the GTV. One of nine [11% (95% CI: 3-45%)] had V(r) which mapped outside of the pretreatment PET-BTV, while 8/9 patients had V(r) within the PET-BTV. Predictors of LRF in our series included GTV volume (p=0.003), but not mean SUV (p=0.13) or max SUV (p=0.25). CONCLUSIONS Following treatment in which the GTV was defined based on the composite of imaging and physical examination, the majority, but not all, LRF occurred within the PET-BTV. These results support an important, but not exclusive, role of FDG-PET in defining the GTV.

Combined-Modality Therapy With Gemcitabine and Radiation Therapy as a Bladder Preservation Strategy: Long-Term Results of a Phase I Trial

PURPOSE A Phase I trial of twice-weekly gemcitabine and concurrent radiation therapy (RT) was performed in patients with muscle-invasive bladder cancer. We present the final analysis of bladder-intact survival (BIS), disease-specific survival (DSS), and overall survival (OS). METHODS AND MATERIALS Eligible patients had muscle-invasive transitional cell carcinoma (cT2-3) and were candidates for cystectomy. Patients underwent maximal transurethral resection of bladder tumor followed by twice-weekly gemcitabine with concurrent RT to the bladder (total of 60 Gy over 6 weeks). Gemcitabine doses ranged from 10 to 33 mg/m(2). RESULTS Median follow-up was 5.6 years (range, 0.6-9.5 years). Twenty-three of 24 patients were evaluable for response. All patients were clinical stage T2. Locoregional failure occurred in seven patients (30%), which were successfully salvaged by radical cystectomy (n = 5) or intravesical therapy (n = 2). Four local failures occurred > 5 years after therapy. Most local failures were noninvasive tumors (Ta or Tis, n = 6). Ten patients (43%) experienced optimal outcome (no failures and bladder intact). The 5-year actuarial estimates of survival are BIS 62%, OS 76%, and DSS 82%. CONCLUSION Twice-weekly gemcitabine with concurrent RT is well tolerated and provides rates of survival and bladder preservation that are comparable to the existing literature. All locoregional failures were successfully salvaged by either radical cystectomy or intravesical therapy. Given the high proportion of late local failures, we recommend long-term monitoring when using this regimen. Future studies comparing the safety and efficacy of gemcitabine- vs. platinum-based bladder preservation protocols are pending.

No Effect of Statins on Biochemical Outcomes After Radiotherapy for Localized Prostate Cancer

OBJECTIVES To examine the effect of concurrent statin use during definitive radiotherapy (RT) on the biochemical outcomes for localized prostate cancer. METHODS A total of 968 patients treated with RT had information about medication use available. Of these, 23% had been taking using statins during RT. Progression-free survival (PFS) was determined by a biochemical failure definition of prostate-specific antigen nadir plus 2 ng/mL, clinical failure, start of androgen deprivation therapy, or death. RESULTS The mean patient age was 68 years. The median radiation dose was 76 Gy. Of the patients, 29% underwent androgen deprivation therapy. The 5-year overall survival rate was 83%. The median PFS time was 7.8 years versus 6.4 years, and the 5-year PFS rate was 70% versus 59% in favor of the statin users (P = 0.03). The analysis by risk group demonstrated no significant statin effect in any of the three risk strata. Stratification by hydrophilic versus hydrophobic statin agents revealed similar results. Multivariate analysis revealed that T stage (P <0.0001), pretreatment prostate-specific antigen level (P <0.0001), and Gleason score (P = 0.0026) were significant predictors of PFS; however, statin use (P = 0.48), androgen deprivation therapy (P = 0.95), pelvic RT (P = 0.96), radiation dose (P = 0.13), age (P = 0.19), and year of treatment (P = 0.07) were not. CONCLUSIONS Statin use did not affect PFS after adjusting for differences in treatment year and multiple prognostic factors. However, T stage, baseline prostate-specific antigen level, and Gleason score were critical determinants of prostate-specific antigen failure. These results did not differ when hydrophilic pravastatin was excluded.

Concurrent Androgen Deprivation Therapy During Salvage Prostate Radiotherapy Improves Treatment Outcomes in High-Risk Patients

PURPOSE To determine whether concurrent androgen deprivation therapy (ADT) during salvage radiotherapy (RT) improves prostate cancer treatment outcomes. METHODS AND MATERIALS A total of 630 postprostatectomy patients were retrospectively identified who were treated with three-dimensional conformal RT. Of these, 441 were found to be treated for salvage indications. Biochemical failure was defined as prostate-specific antigen (PSA) of 0.2 ng/mL or greater above nadir with another PSA increase or the initiation of salvage ADT. Progression-free survival (PFS) was defined as the absence of biochemical failure, continued PSA rise despite salvage therapy, initiation of systemic therapy, clinical progression, or distant failure. Multivariate-adjusted Cox proportional hazards modeling was performed to determine which factors predict PFS. RESULTS Low-, intermediate-, and high-risk patients made up 10%, 24%, and 66% of patients, respectively. The mean RT dose was 68 Gy. Twenty-four percent of patients received concurrent ADT (cADT). Regional pelvic nodes were treated in 16% of patients. With a median follow-up of 3 years, the 3-year PFS was 4.0 years for cADT vs. 3.4 years for cADT patients (p = 0.22). Multivariate analysis showed that concurrent ADT (p = 0.05), Gleason score (p < 0.001), and pre-RT PSA (p = 0.03) were independent predictors of PFS. When patients were stratified by risk group, the benefits of cADT (hazard ratio, 0.65; p = 0.046) were significant only for high-risk patients. CONCLUSIONS This retrospective study showed a PFS benefit of concurrent ADT during salvage prostate RT. This benefit was observed only in high-risk patients.

Limited-stage extrapulmonary small cell carcinoma: Outcomes after modern chemotherapy and radiotherapy

Background:The purpose of this study was to determine the clinical outcomes and patterns of failure of limited-stage extrapulmonary small cell carcinoma (EPSCC) treated with modern chemotherapy and radiation (RT). Methods:We retrospectively identified 18 patients with limited-stage EPSCC treated definitively with three-dimensional conformal RT or intensity modulated radiation therapy and chemotherapy. Patients were treated between November 1987 and May 2006. Primary sites of disease included head and neck (n = 7), genitourinary (n = 7), gynecologic (n = 3), and gastrointestinal (n = 1). Chemotherapy consisted of combined platinum and etoposide in 88% of patients. The median number of chemotherapy cycles was 4 (range 3–6), and the median RT dose was 62 Gy (range 32.4–85 Gy). No patient received prophylactic cranial radiation. Results:With a median follow-up for all patients of 14 months (range 4–42 months), the median overall survival was 17 months, and median disease-free survival was 6 months. Eleven percent (2 of 18) of patients had a locoregional failure, and 78% (14 of 18) had a distant failure. One of these patients had a brain failure. There were no significant differences between the overall survival for patients with gynecologic, head and neck, and genitourinary disease. Conclusions:Despite modern chemotherapy and RT, patients with limited-stage EPSCC do poorly. Consistent with previous findings the majority of the first failures are distant. Brain failures in this series were uncommon despite no prophylactic cranial radiation. These findings support the need for further studies in an attempt to improve systemic therapies for this disease.

Impact of Common Iliac Nodal Treatment on Radiation Outcomes in Localized Prostate Cancer

OBJECTIVES The Radiation Therapy Oncology Group 9413 trial has shown an improvement in progression-free survival (PFS) with external beam radiotherapy that included the pelvic nodes. In clinical practice, two pelvic field size designs are in use. We examined the effect of differences in the level of pelvic nodal coverage using three-dimensional conformal radiotherapy on biochemical failure-free survival (BFFS) and PFS in early-stage prostate cancer. METHODS The patients were identified retrospectively who had undergone whole pelvis (WP) or minipelvis (MP) three-dimensional conformal radiotherapy. Biochemical failure was defined as the nadir prostate-specific antigen (PSA) level plus 2 ng/mL. RESULTS Of the 669 patients identified, 384 had undergone MP (57%) and 285 WP (42%) treatment, with a median PSA follow-up of 56 months. Of the 669 patients, 11%, 35%, and 54% were at low, intermediate, and high risk, respectively. The median dose was 75 Gy for the MP and 71 Gy for the WP groups. Of the MP and WP groups, 52% and 36% underwent hormonal therapy. The median BFFS and 5-year BFFS rate was 128 months and 73% for the MP group and 96 months and 58% for the WP group. The median PFS and 5-year PFS rate was 128 months and 72% for the MP group and 83 months and 56% for the WP group. Multivariate analysis revealed no difference between MP and WP treatment. However T stage, pretreatment PSA level, and Gleason score were significant predictors of BFFS and PFS. CONCLUSIONS We observed no difference in outcomes between patients undergoing WP versus MP using three-dimensional conformal radiotherapy. Therefore, the exclusion of the common iliac lymph nodes in the treatment of patients with high-risk prostate cancer might be acceptable.

Determining if pretreatment PSA doubling time predicts PSA trajectories after radiation therapy for localized prostate cancer

INTRODUCTION To determine if pretreatment PSA doubling time (PSA-DT) can predict post-radiation therapy (RT) PSA trajectories for localized prostate cancer. MATERIALS AND METHODS Three hundred and seventy-five prostate cancer patients treated with external beam RT without androgen deprivation therapy (ADT) were identified with an adequate number of PSA values. We utilized a linear mixed model (LMM) analysis to model longitudinal PSA data sets after definitive treatment. Post-treatment PSA trajectories were allowed to depend on the pre-RT PSA-DT, pre-RT PSA (iPSA), Gleason score (GS), and T-stage. RESULTS Pre-RT PSA-DT had a borderline impact on predicting the rate of PSA rise after nadir (p=0.08). For a typical low risk patient (T1, GS6, iPSA 10), the predicted PSA-DT post-nadir was 21% shorter for pre-RT PSA-DT<24month compared to pre-RT PSA-DT>24month (19month vs. 24month). Additional significant predictors of post-RT PSA rate of rise included GS (p<0.0001), iPSA (p<0.0001), and T-stage (p=0.02). CONCLUSIONS We observed a trend between rapidly rising pre-RT PSA and the post-RT post-nadir PSA rise. This effect appeared to be independent of iPSA, GS, or T-stage. The results presented suggest that pretreatment PSA-DT may help predict post-RT PSA trajectories.

Predicting biochemical failure and overall survival through intratherapy PSA changes during definitive external beam radiotherapy.

PURPOSE To determine whether intratherapy prostate-specific antigen (itPSA) changes during radiotherapy (RT) predict prostate cancer outcomes. METHODS AND MATERIALS We retrospectively identified patients treated with definitive external beam RT without hormonal therapy who had at least two itPSA measurements. We calculated the adjusted ratio of rise (ARR) in itPSA relative to the pretreatment baseline PSA for each patient. This was defined as ln(maximal itPSA + 1)/ln(baseline PSA + 1). We stratified patients according to an ARR of <1 vs. >1.1. This corresponded to an approximately <30% vs. >30% increase in PSA during RT. Univariate and multivariate analyses were performed examining for biochemical failure-free survival (BFFS) and overall survival (OS). RESULTS At a median follow-up of 74 months, we identified 307 patients who met our criteria. Univariate analysis revealed that patients with an ARR of <1.1 (n = 182) had statistically significant inferior BFFS and OS compared with those with an ARR of >1.1 (n = 125). The median BFFS and OS for these two groups was 51 vs. 101 months (p = 0.001) and 96 vs. 128 months (p = 0.01), respectively. On multivariate analysis, the effect of ARR on the risk of biochemical failure for patients with an ARR of <1.1 was significant (p = 0.03) only during the first year after RT. In contrast, the effect of the ARR on OS remained significant for a full 5 years (p = 0.05). CONCLUSION The results of our study have shown that an ARR of <1.1 predicts for inferior BFFS and OS in patients treated with RT alone. PSA measurement during RT is a novel clinical tool that could be used to identify patients who might warrant more aggressive therapeutic intervention.