Ten-year outcome including patterns of failure and toxicity for adjuvant whole abdominopelvic irradiation in high-risk and poor histologic feature patients with endometrial carcinoma.

PURPOSE: To evaluate the long-term results of treatment using adjuvant whole abdominal irradiation (WAPI) with a pelvic/vaginal boost in patients with Stage I-III endometrial carcinoma at high risk of intra-abdominopelvic recurrence, including clear cell (CC) and serous-papillary (SP) histologic features. METHODS AND MATERIALS: In a prospective nonrandomized trial, 119 patients were treated with adjuvant WAPI between November 1981 and April 2000. All patients were analyzed, including those who did not complete therapy. The mean age at diagnosis was 66 years (range 39-88). Thirty-eight patients (32%) had 1989 FIGO Stage I-II disease and 81 (68%) had Stage III. The pathologic features included the following: 64 (54%) with deep myometrial invasion, 48 (40%) with positive peritoneal cytologic findings, 69 (58%) with high-grade lesions, 21 (18%) with positive pelvic/para-aortic lymph nodes, and 44 (37%) with SP or CC histologic findings. RESULTS: The mean follow-up was 5.8 years (range 0.2-14.7). For the entire group, the 5- and 10-year cause-specific survival (CSS) rate was 75% and 69% and the disease-free survival (DFS) rate was 58% and 48%, respectively. When stratified by histologic features, the 5- and 10-year CSS rate for adenocarcinoma was 76% and 71%, and for serous papillary/CC subtypes, it was 74% and 63%, respectively (p = 0.917). The 5- and 10-year DFS rate for adenocarcinoma was 60% and 50% and was 54% and 37% serous papillary/CC subtypes, respectively (p = 0.498). For surgical Stage I-II, the 5-year CSS rate was 82% for adenocarcinoma and 87% for SP/CC features (p = 0.480). For Stage III, it was 75% and 57%, respectively (p = 0.129). Thirty-seven patients had a relapse, with the first site of failure the abdomen/pelvis in 14 (38%), lung in 8 (22%), extraabdominal lymph nodes in 7 (19%), vagina in 6 (16%), and other in 2 (5%). When stratified by histologic variant, 32% of patients with adenocarcinoma and 30% with the SP/CC subtype developed recurrent disease. Most failures for either histologic group occurred within the abdominopelvic region. However, one-third of the adenocarcinoma recurrences were in the lung. Multivariate regression analysis (age, surgical stage, grade, myometrial invasion, histologic type, lymph node status, and peritoneal cytology) demonstrated age (p = 0.019) and surgical stage (p = 0.036) to be of prognostic significance for CSS; age (p = 0.036) was the only significant prognostic factor for DFS. Grade 1-2 gastrointestinal and hematologic acute toxicities were common. Asymptomatic bibasilar scarring on chest X-ray and mild elevation of liver enzymes were seen in almost 50% of the patients. Even though chronic toxicities were less frequent, 12% developed Grade 3-4 gastrointestinal and 2% Grade 3 renal toxicities. CONCLUSION: Adjuvant WAPI is very effective treatment with excellent 10-year results for Stage I-III endometrial carcinoma with risk factors for intra-abdominopelvic recurrence, including SP or CC histologic variants, deep myometrial invasion, high grade, nodal involvement, and positive peritoneal cytology. The low long-term complication rate with high CSS rate makes WAPI the treatment of choice for these patients with significant comorbidities.

Pathologic evidence of dose-response and dose-volume relationships for prostate cancer treated with combined external beam radiotherapy and high-dose-rate brachytherapy.

PURPOSE: The clinical significance of postradiotherapy (RT) prostate biopsy characteristics is not well understood relative to the known prognostic factors. We performed a detailed pathologic review of posttreatment biopsy specimens in an attempt to clarify their relationship with clinical outcome and radiation dose. METHODS AND MATERIALS: Between 1991 and 1998, 78 patients with locally advanced prostate cancer were prospectively treated with external beam RT in combination with high-dose-rate brachytherapy at William Beaumont Hospital and had post-RT biopsy material available for a complete pathologic review. Patients with any of the following characteristics were eligible for study entry: pretreatment prostate-specific antigen level > or =10.0 ng/mL, Gleason score > or =7, or clinical Stage T2b-T3cN0M0. Pelvic external beam RT (46.0 Gy) was supplemented with three (1991-1995) or two (1995-1998) ultrasound-guided transperineal interstitial (192)Ir high-dose-rate implants. The brachytherapy dose was escalated from 5.50 to 10.50 Gy per implant. Post-RT prostate biopsies were performed per protocol at a median interval of 1.5 years after RT. All pre- and post-RT biopsy specimen slides from each case were reviewed by a single pathologist (N.S.G.). The presence and amount of residual cancer, most common RT-effect score, and least amount RT-effect score were analyzed. The median follow-up was 5.7 years. Biochemical failure was defined as three consecutive prostate-specific antigen rises. RESULTS: Forty patients (51%) had residual cancer in the post-RT biopsies. The 7-year biochemical control rate was 79% for patients with negative biopsies vs. 62% for those with positive biopsies with marked RT damage vs. 33% for those with positive biopsies with no or minimal RT damage. A greater percentage of positive pre-RT biopsy cores (p = 0.01), lower total RT dose (p = 0.001), lower dose per implant (p = 0.001), and greater percentage of positive post-RT biopsy cores (p = 0.01) were each associated with biochemical failure (Cox regression, univariate analysis). For patients with <25% positive post-RT biopsy cores, the 7-year biochemical control rate was 81% vs. a 62% biochemical control rate for those with 25-49% positive cores and only 32% for those with > or =50% positive cores (p = 0.01). On Cox multiple regression analysis, only the percentage of positive pre-RT biopsy cores and RT dose remained significantly associated with biochemical failure. Of all the factors analyzed, only the pretreatment cancer volume and lower RT dose were significantly associated with residual cancer and/or residual cancer with no or minimal RT damage. A greater percentage of positive pre-RT biopsy cores was associated with both a positive post-RT biopsy (p = 0.08) and a greater percentage of positive post-RT biopsy cores (p = 0.04). A lower total RT dose was associated with both a positive post-RT biopsy (p = 0.08) and a greater percentage of positive post-RT biopsy cores (p = 0.02). For patients who received <80 Gy (equivalent in 2-Gy fractions), 73% had positive post-RT biopsies vs. a 56% biopsy positivity rate for those who received 84-90 Gy and only 39% for those who received > or =92 Gy (p = 0.07). CONCLUSION: Patients with positive post-RT biopsies are more likely to experience biochemical failure, especially when the RT damage is minimal. Patients who have a larger pretreatment tumor volume or receive a lower RT dose are more likely to demonstrate post-RT biopsy positivity and biochemical failure.

Dose escalation using conformal high-dose-rate brachytherapy improves outcome in unfavorable prostate cancer.

PURPOSE: To overcome radioresistance for patients with unfavorable prostate cancer, a prospective trial of pelvic external beam irradiation (EBRT) interdigitated with dose-escalating conformal high-dose-rate (HDR) prostate brachytherapy was performed. METHODS AND MATERIALS: Between November 1991 and August 2000, 207 patients were treated with 46 Gy pelvic EBRT and increasing HDR brachytherapy boost doses (5.50-11.5 Gy/fraction) during 5 weeks. The eligibility criteria were pretreatment prostate-specific antigen level >or=10.0 ng/mL, Gleason score >or=7, or clinical Stage T2b or higher. Patients were divided into 2 dose levels, low-dose biologically effective dose <93 Gy (58 patients) and high-dose biologically effective dose >93 Gy (149 patients). No patient received hormones. We used the American Society for Therapeutic Radiology and Oncology definition for biochemical failure. RESULTS: The median age was 69 years. The mean follow-up for the group was 4.4 years, and for the low and high-dose levels, it was 7.0 and 3.4 years, respectively. The actuarial 5-year biochemical control rate was 74%, and the overall, cause-specific, and disease-free survival rate was 92%, 98%, and 68%, respectively. The 5-year biochemical control rate for the low-dose group was 52%; the rate for the high-dose group was 87% (p <0.001). Improvement occurred in the cause-specific survival in favor of the brachytherapy high-dose level (p = 0.014). On multivariate analysis, a low-dose level, higher Gleason score, and higher nadir value were associated with increased biochemical failure. The Radiation Therapy Oncology Group Grade 3 gastrointestinal/genitourinary complications ranged from 0.5% to 9%. The actuarial 5-year impotency rate was 51%. CONCLUSION: Pelvic EBRT interdigitated with transrectal ultrasound-guided real-time conformal HDR prostate brachytherapy boost is both a precise dose delivery system and a very effective treatment for unfavorable prostate cancer. We demonstrated an incremental beneficial effect on biochemical control and cause-specific survival with higher doses. These results, coupled with the low risk of complications, the advantage of not being radioactive after implantation, and the real-time interactive planning, define a new standard for treatment.

Implementation of an oncology exercise and wellness rehabilitation program to enhance survivorship: the Beaumont Health System experience.

We developed a multidisciplinary approach to oncology rehabilitation by setting up a physical therapy screening program in a dedicated multidisciplinary clinic to improve survivorship care in the community oncology setting. In June 2011, an oncology rehabilitation program was launched as part of the overall survivorship program to provide patients with an introduction to cancer services, consultation with multiple clinicians, education about their diagnoses, and recommendation for rehabilitation services during or after treatment. The consultation was in conjunction with specialists at the multidisciplinary clinics that were already established within the organization. A dedicated and trained oncology physical therapist participated in the comprehensive multidisciplinary discussion. From the beginning of the program in June 2011 until December 2012, 288 patients (231 women and 57 men) entered the oncology exercise and wellness rehabilitation program. The establishment of the program improved the quality of care for cancer patients as demonstrated by the number of patients screened before treatment recommendations. The program also served the need for continued health and wellness for those in survivorship.

Impact of the number of cautionary and/or unsuitable risk factors on outcomes after accelerated partial breast irradiation.

PURPOSE: To examine clinical outcomes of accelerated partial-breast irradiation (APBI) stratified by the number of American Society for Radiation Oncology consensus statement cautionary/unsuitable risk factors (RFs) present. METHODS AND MATERIALS: A total of 692 patients were treated with APBI at a single institution between April 1993 and January 2012 using interstitial (n=195), balloon (n=292), and 3-dimensional conformal radiation therapy (n=205) techniques. Clinical outcomes were evaluated by risk group and number of RFs. RESULTS: Median follow-up was 5.2 years (range, 0-18.3 years). Most patients were classified as suitable (n=240, 34%) or cautionary (n=343, 50%) risk, whereas 16% (n=109) were unsuitable. In patients with increasing total RFs (1 RF, 2 RF, 3+ RF), higher rates of grade 3 histology (10% vs 18% vs 32%, P<.001), estrogen receptor negativity (0 vs 12% vs 29%, P<.001), close/positive margins (0 vs 6% vs 17%, P<.001), and use of adjuvant chemotherapy (3% vs 12% vs 33%, P<.001) were noted. When pooling cautionary and unsuitable patients, increased ipsilateral breast tumor recurrence/regional recurrence was most notable for patients with 3 or more combined RFs versus 2 or fewer combined RFs (P<.001). CONCLUSIONS: Patients with 3 or more cautionary or unsuitable RFs may be at risk for higher local, regional, and distant recurrence after breast-conserving therapy using APBI. Patients with 2 or fewer total RFs have 98% locoregional control at 5 years. Inclusion of total number of RFs in future risk stratification schemes for APBI may be warranted.

Prostate volume reduction with androgen deprivation therapy before interstitial brachytherapy.

PURPOSE: We assessed the degree of prostate downsizing using androgen deprivation, and determined its relation to clinical and pathological variables. MATERIALS AND METHODS: From June 1994 to January 2000, 107 patients with prostate cancer received androgen deprivation before interstitial brachytherapy at our hospital. All charts were reviewed for clinical, pathological and treatment related variables. Prostate volume was measured using transrectal ultrasound. All variables were analyzed with regard to the degree of prostate downsizing. RESULTS: Mean percent volume reduction of the prostate was 33% after a 3.7-month average duration of androgen deprivation. Larger prostate volume before androgen deprivation and longer deprivation duration statistically correlated with mean percent volume reduction. Simple linear and multiple regression analyses revealed that these 2 variables remained significant predictors of percent volume reduction. Subgroup analysis indicated that a significant difference was seen in patients who received androgen deprivation with luteinizing hormone releasing hormone agonists alone versus those who received treatment with total androgen blockade (luteinizing hormone releasing hormone agonists plus antiandrogens 30% versus 35%, p = 0.04), and when prostate volume before androgen deprivation was less than 50 cc versus larger volumes (30% versus 35%, p = 0.01). Of patients with an initial prostate volume of greater than 50 cc 82% achieved a volume of less than 50 cc after androgen deprivation therapy. CONCLUSIONS: Androgen deprivation therapy before brachytherapy is a method of downsizing the prostate to overcome anatomical limitations, including larger gland volume and pubic arch interference.

Acute and subacute toxicity associated with concurrent adjuvant radiation therapy and paclitaxel in primary breast cancer therapy.

The purpose of this study was to describe the toxicity of concurrent standard dose adjuvant radiation therapy (RT) and paclitaxel in a series of patients receiving primary breast cancer therapy. From June 1998 to April 1999, 20 patients with breast cancer received concurrent adjuvant radiation and paclitaxel. There were 16 patients (80%) with American Joint Committee on Cancer (AJCC) stage II disease and 4 with stage III disease. Eighteen patients, 12 postmastectomy and 6 breast conservation, were treated with definitive surgery followed by concurrent RT and paclitaxel. Two received concurrent neoadjuvant radiation and paclitaxel. All patients received a doxorubicin-containing combination prior to radiation and paclitaxel. RT was delivered concurrently with paclitaxel after the completion of all doxorubicin therapy, with all patients receiving at least two cycles of paclitaxel (175 mg/m2) every 3 weeks during RT. Toxicity was graded weekly according to Radiation Therapy Oncology Group criteria. Thirteen patients (65%) developed grade 2 or higher cutaneous toxicity. In the postmastectomy group, 6 of 12 patients (50%) developed grade 2 cutaneous toxicity, and 4 of 12 patients (33%) developed grade 3. RT was discontinued in 1 and placed on hold in 3 of these patients. In the breast-conservation group, 2 of 6 patients (33%) developed grade 3 toxicity. In the neoadjuvant group, 1 of 2 patients (50%) developed grade 3 toxicity. Four patients (20%) developed radiation pneumonitis, 2 of 12 (17%) in the postmastectomy group and 2 of 6 (33%) in the breast conservation group, with 2 requiring hospitalization and 1 a diagnostic open-lung biopsy. In this group of patients, standard dose concurrent radiation and paclitaxel resulted in a high incidence of cutaneous and pulmonary toxicity. Concurrent radiation and paclitaxel with these doses and schedule should be approached cautiously until further studies documenting its safety are completed.

Improved outcome at 10 years for serous-papillary/clear cell or high-risk endometrial cancer patients treated by adjuvant high-dose whole abdomino-pelvic irradiation.

PURPOSE: The aim of the study was to evaluate the 10-year treatment outcome of utilizing adjuvant high-dose whole abdominal irradiation (WAPI technique) with a pelvic/vaginal boost in patients with stage I-III endometrial carcinoma at high risk for intra-abdominopelvic recurrence, including serous-papillary and clear cell histologies. MATERIAL AND METHODS: In a prospective nonrandomized trial, 132 patients were treated with adjuvant WAPI between November 1981 and October 2001. Forty-three patients (32%) were 1998 FIGO stage I-II and 89 (68%) were stage III. Pathological features included the following: 66 (52%) with deep myometrial invasion, 50 (38%) with positive peritoneal cytology, 89 (67%) with high-grade lesions, 25 (19%) with positive pelvic/para-aortic lymph nodes, and 58 (45%) with serous-papillary or clear cell histology. RESULTS: The mean follow up was 6.4 years (range 0.6-16.1). For the entire group, the 5- and 10-year cause-specific survival (CSS) was 77 and 72%, whereas the disease-free survival (DFS) was 55 and 45%. When stratified by histology the 5- and 10-year CSS for adenocarcinoma was 75 and 70%, while serous-papillary/clear cell was 80 and 74% (P = 0.314). The 5- and 10-year DFS for adenocarcinoma was 59 and 49%, whereas serous-papillary/clear cell was 49 and 38% (P = 0.563). For surgical stages I-II, the 5-year CSS was 83% for adenocarcinoma and 89% for serous-papillary (P = 0.353). For stage III, it was 73 and 62% (P = 0.318), respectively. Forty-six patients (35%) relapsed. The first site of failure was the abdomen/pelvis in 27/46 (59%). When stratified by histologic variant, 34% of patients with adenocarcinoma and 41% with serous-papillary developed recurrent disease. In multivariate regression analysis only advancing age was of prognostic significance for CSS (P = 0.025) and DFS (P = 0.026). Chronic grade 3/4 GI toxicity was seen in 14%, and 2% of patients developed grade 3 renal toxicity. CONCLUSION: High-dose adjuvant WAPI is very effective treatment with excellent 10-year results for stage I-III endometrial carcinoma with risk factors for intra-abdominopelvic recurrence, including serous-papillary or clear cell histology. The low long-term complication rate with high CSS makes high-dose WAPI the treatment of choice for these patients with significant comorbidities.