Leayn Flaherty

Treatment of locally advanced unresectable pancreatic cancer: a 10-year experience

PURPOSE We retrospectively analyzed the results of patients with locally advanced unresectable pancreatic cancer (LAPC) treated with either chemoradiation (CRT) or chemotherapy alone over the past decade. METHODS AND MATERIALS Between December 1998 and October 2009, 116 patients with LAPC were treated at our institution. Eighty-four patients received concurrent chemoradiation [RT (+) group], primarily 5-flourouracil based (70%). Thirty-two patients received chemotherapy alone [RT (-) group], the majority gemcitabine based (78%). Progression-free survival (PFS) and overall survival (OS) were calculated from date of diagnosis to date of first recurrence and to date of death or last follow-up, respectively. Univariate statistical analysis was used to determine significant prognostic factors for overall survival. RESULTS Median patient age was 67 years. Sixty patients were female (52%). Median follow-up was 11 months (range, 1.6-59.4 months). The RT (+) group received a median radiation dose of 50.4 Gy, was more likely to present with ECOG 0-1 performance status, and experienced less grade 3-4 toxicity. PFS was 10.9 versus 9.1 months (P=0.748) and median survival was 12.5 versus 9.1 months (P=0.998) for the RT (+) and RT (-) groups respectively (P=0.748). On univariate analysis, patients who experienced grade 3-4 toxicity had worse overall survival than those who did not (P=0.02). CONCLUSIONS Optimal management for LAPC continues to evolve. Patients who developed treatment-related grade 3-4 toxicity have a poorer prognosis. Survival rates were not statistically significant between chemotherapy and chemoradiotherapy groups.

Change in CA 19-9 levels after chemoradiotherapy predicts survival in patients with locally advanced unresectable pancreatic cancer

PURPOSE RTOG 9704 demonstrated a prognostic role for postoperative CA 19-9 in patients with resectable pancreatic carcinoma following surgery. Our study aimed to investigate whether CA 19-9 provided similar prognostic information in patients with locally advanced unresectable pancreatic cancer (LAPC) treated with chemoradiotherapy (CRT) and to determine whether such endpoints should therefore be reported in future randomized trials. METHODS AND MATERIALS Between December 1998 and October 2009, 253 patients with LAPC were treated with 5-fluourouracil-based concurrent CRT at our institution. Median radiation dose was 50.4 Gy. Only patients with a bilirubin of less than 2 mg/dL at the time the CA 19-9 was evaluated were included in the analysis to avoid the confounding effect of hyperbilirubinemia. Of the eligible patients, 54 had pre and post CRT CA 19-9 values available. The median age was 68 years and 52% were female. Categorized versions of the first post-CRT CA 19-9 were tested in 50 point increments beginning at <50 to >1,000 and percent change in pre to post-CRT CA 19-9 using cut points of 10% increments from <0% (increased) to >90%. Survival was measured from the date of first post CRT CA 19-9 level until death or last follow-up. Univariate and multivariate statistical methodologies were used to determine significant prognostic factors for overall survival. RESULTS Median CA 19-9 prior to CRT was 363 U/mL and post CRT median was 85.5 U/mL. Following CRT, patients with a decrease of >90% from their baseline CA 19-9 level had a significantly improved median survival than those that did not (16.2 vs. 7.5 months, P=0.01). The median survival of patients with a CA 19-9 level lower than the median post CRT value was 10.3 months, compared with 7.1 months for those with a CA 19-9 level greater than the median (P=0.03). Post CRT CA 19-9 less than 50 U/mL and histologic grade I-II also showed prognostic significance (both P=0.03). In multivariate analysis, post CRT CA 19-9 less than the median level of 85.5 U/mL was an independent prognostic factor for overall survival (HR 0.34; 95% CI, 0.13-0.85, P=0.02). CONCLUSIONS Our results indicate that post treatment CA 19-9 is predictive for overall survival in patient with LAPC following CRT. We recommend that pre and post treatment CA 19-9 levels be obtained in patients receiving CRT and that these values be considered for prognostic nomograms and future clinical trials.

ANALYSIS OF CLINICAL AND DOSIMETRIC FACTORS ASSOCIATED WITH CHANGE IN RENAL FUNCTION IN PATIENTS WITH GASTROINTESTINAL MALIGNANCIES AFTER CHEMORADIATION TO THE ABDOMEN

PURPOSE To analyze clinical and dosimetric factors associated with change in renal function in patients with gastrointestinal malignancies after chemoradiation to the abdomen. METHODS AND MATERIALS A retrospective review of 164 patients with gastrointestinal malignancies treated between 2002 and 2007 was conducted to evaluate change in renal function after concurrent chemotherapy and three-dimensional conformal abdominal radiotherapy (RT). Laboratory and biochemical endpoints were determined before RT and after RT at 6-month intervals. Factors assessed included smoking, diabetes, hypertension, blood urea nitrogen, creatinine, creatinine clearance (CrCl), chemotherapy, and dose-volume parameters. Renal toxicity was assessed by decrease in CrCl and scored using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late radiation morbidity scoring schema. RESULTS Of 164 patients, 63 had clinical and dosimetric data available. Median follow-up was 17.5 months. Creatinine clearance declined from 98.46 mL/min before RT to 74.20 mL/min one year after chemoradiation (p < 0.0001). Mean decrease in CrCl was 21.37%. Pre-RT CrCl, percentage of bilateral renal volume receiving at least 10 Gy (V(10)), and mean kidney dose were significantly associated with development of Grade > or =2 renal complications at 1 year after chemoradiation (p = 0.0025, 0.0170, and 0.0095, respectively). CONCLUSIONS We observed correlation between pre-RT CrCl, V(10), and mean kidney dose and decline in CrCl 1 year after chemoradiation. These observations can assist in treatment planning and renal dose constraints in patients receiving chemotherapy and abdominal RT and may help identify patients at increased risk for renal complications.

Neoadjuvant chemoradiotherapy for esophageal/gastroesophageal carcinoma.

BACKGROUND Esophageal/gastroesophageal junction (GEJ) adenocarcinoma is increasingly treated with trimodality therapy. We present our experience using carboplatin/paclitaxel and radiotherapy followed by surgery. METHODS Consecutive patients with distal esophageal/GEJ adenocarcinoma (≥T2 or N+) treated from July 2010 to October 2011 were identified. Treatment included neoadjuvant carboplatin/paclitaxel with concurrent radiotherapy (CRT) to 50.4 Gy using an IMRT technique and then Ivor Lewis esophagogastrectomy (ILE). PET/CT was performed prior to and after CRT. Patient/treatment characteristics and tumor response were analyzed. RESULTS Over this timeframe, 16 patients completed trimodality therapy. All were male, median age of 60 years (45-72 years). All tumors were grade 2-3 with mean tumor length of 4.4 cm (1-9 cm). A median of 6 cycles (5-9 cycles) neoadjuvant carboplatin/paclitaxel were administered. Average time from diagnosis to CRT completion was 76 days (44-141 days) and 60 days (35-92 days) from CRT end to surgery. Neoadjuvant CRT was well tolerated with mean weight loss of 3.9 kg. All pts had R0 resections. No anastomotic leaks or perioperative mortality occurred. Mean hospital stay was 13 days (8-28 days). Pathologic complete response (pCR) was seen in 38% of patients, microscopic residual disease (isolated tumor cells or <2 mm) in 31%, and macroscopic residual disease remained in 31%. Mean SUV reduction was 41% (0-100%). Of 11 patients with ≥35% SUV decrease, 45% had pCR and 27% had microscopic residual disease. Three patients had signet ring features. Of these, 2 had no SUV reduction and all had gross residual disease, including the only patient with positive nodal disease. CONCLUSIONS Trimodality therapy utilizing concurrent carboplatin/paclitaxel and radiotherapy to 50.4 Gy followed by surgery was well tolerated and resulted in significant pathologic complete response or minimal residual disease. Further investigation of predictive factors for response is needed to best tailor therapy in the management of esophageal/GEJ adenocarcinoma.

Association of Technetium99m MAG-3 renal scintigraphy with change in creatinine clearance following chemoradiation to the abdomen in patients with gastrointestinal malignancies

BACKGROUND Information on differential renal function following abdominal chemoradiation is limited. This study evaluated the association between renal function as measured by biochemical endpoints and scintigraphy and dose volume parameters in patients with gastrointestinal malignancies. MATERIALS AND METHODS Patients who received abdominal chemoradiation between 2002 and 2009 were identified for this study. Technetium(99m) MAG-3 scintigraphy and laboratory data were obtained prior to and after chemoradiation in 6 month intervals. Factors assessed included age, gender, hypertension, diabetes, and dose volume parameters. Renal function was assessed by biochemical endpoints and renal scintigraphy. RESULTS Significant reductions in relative renal function of the primarily irradiated kidney and creatinine clearance were seen. Split renal function decreased from 49.75% pre-radiation to 47.74% and 41.28% at 6-12 months and >12 months post-radiation (P=0.0184). Creatinine clearance declined from 90.67ml/min pre-radiation to 82.23ml/min and 74.54ml/min at 6-12 months and >12 months post-radiation (P<0.0001). Univariate analysis of patients who had at least one post-radiation renogram showed the percent volumes of the primarily irradiated kidney receiving ≥ 25 Gy (V(25)) and 40 Gy (V(40)) were significantly associated with ≥5% decrease in relative renal function (P=0.0387 and P=0.0438 respectively). CONCLUSION Decline in split renal function using Technetium(99m) MAG-3 scintigraphy correlates with decrease in creatinine clearance and radiation dose-volume parameters following abdominal chemoradiation. Change in split perfusion can be detected as early as 6 months post-radiation. Scintigraphy may provide early determination and quantification of subclinical renal injury prior to clinical evidence of nephropathy.

Long-term outcome of stage I seminoma.

Purpose:To report on long-term outcomes among patients with stage I seminoma treated by orchiectomy with or without adjuvant radiation. Materials and Methods:A retrospective review of medical records of patients treated between 1974 and 2002 was undertaken to identify factors associated with patient outcomes. Results:With a median follow-up of 7.7 years, 80% (4 of 5) of the surveillance group experienced a disease relapse, while only 3% (2 of 70) in the radiation therapy group had disease relapse. This difference in relapse rates was statistically significant, but there was no significant difference in overall survival between the 2 groups. There was a significant relationship between patient age and disease relapse, whereby all of the relapses were seen in patients younger than 36 years at diagnosis (P = 0.03). Of the total 75 patients, 7 (9%) developed second primary tumors. Six of them (6 of 7) were treated with adjuvant radiation, and 1 patient (1 of 7) was on surveillance. Conclusion:In this study, risk of relapse was significantly associated with surveillance and in patients younger than 36 years at diagnosis. These results suggest that surveillance can only be safely adopted for patients who can be followed up closely. We consider adjuvant radiation a very effective choice despite the low risk of associated secondary malignancies.

Pure Tubular Breast Carcinoma: A 34 year Study of Outcomes

To the Editor: Tubular carcinoma of the breast is a rare, well-differentiated variant of invasive ductal carcinoma which is thought to carry an excellent prognosis (1–3). The purpose of this study is to review the Roswell Park Cancer Institute experience with tubular breast cancers. Between September of 1971 and January 2004, 8,832 patients were treated for both invasive and noninvasive breast cancer, and 44 (0.5%) were coded as tubular carcinoma or invasive ductal carcinoma with tubular features. Tumors were considered tubular only if the pathology report specifically identified the histology as tubular carcinoma, and did not include a description of other histologic types. This process identified 27 of the 44 cases as tubular cancers, while 17 were considered of mixed tubular or other histology. Staging was according to the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 6th edition (4). Patient follow-up time was calculated using the potential follow-up method (5). The Kaplan–Meier method was used to derive survival probabilities (6). The mean patient age was 59.3 years and all patients were Caucasian. Seventy-eight percent (21 ⁄ 27) of patients had stage I disease, while 19% (5 ⁄ 27) had stage IIA disease, and 4% (1 ⁄ 27) was stage IIIA. Forty-one percent (11 ⁄ 27) of patients had a first-degree relative with breast or ovarian cancer. The initial detection of a breast tumor was made by mammogram in 52% (14 ⁄ 27) of cases, while a mass was palpated by the patient or a physician in 37% (10 ⁄ 27) of cases. Tumor characteristics are summarized in Table 1. The mean tumor diameter was 1.09 cm (range, 0.2–4.2 cm). The majority of patients, who had lymph nodes assessed by either axillary node dissection or a sentinel node biopsy, had no positive lymph nodes on presentation (84%), while 11% (2 ⁄ 19) had 1–3 positive nodes and 5% (1 ⁄ 19) had four positive axillary node metastases. Ductal carcinoma in situ was reported in 59% (16 ⁄ 27) of patients. All patients who had hormone receptor status assessed (16 ⁄ 16) were estrogen receptor (ER) positive, while the majority of patients (10 ⁄ 14) were also progesterone receptor positive. The upper outer quadrant was the site of occurrence in 67% (18 ⁄ 27) of patients and with 89% (24 ⁄ 27) of patients having unifocal disease and 11% (3 ⁄ 27) of patients having multifocal distribution. Seventy-four percent (20 ⁄ 27) of patients were treated with breast-conserving surgery, while 22% (6 ⁄ 27) underwent modified radical mastectomy (MRM), and one patient received no additional surgery after biopsy. In the post-operative setting, one third of patients (9 ⁄ 27) received no adjuvant treatment. Over half (15 ⁄ 27) of patients received post-operative radiation (XRT), 14 of which had undergone a previous breast conserving surgery, and one of which had a previous MRM. Thirty percent of patients (8 ⁄ 27) had XRT alone in the adjuvant setting, while 19% (5 ⁄ 27) receive a combination of XRT and hormonal therapy (HT), and 7% (2 ⁄ 27) received XRT and HT in combination with systemic chemotherapy. Eleven percent (3 ⁄ 27) of patients received HT alone in the adjuvant setting. With a median follow-up period was 5.3 years (range; <1–24 years), none of the patients had evidence of either local or systemic recurrence, and no patients had died of breast cancer. Seventy-eight percent (21 ⁄ 27) of patients were alive at the time of last follow-up and 22% (6 ⁄ 27) had died of other causes not related to breast cancer. Of patients with at least five-years of follow-up, overall survival at 5-years was 89% (16 ⁄ 18) while for those with at least 10-year follow-up, overall survival is 70% (7 ⁄ 10). Twenty-two percent of patients (6 ⁄ 27) were diagnosed with a second cancer, two of which developed infiltrating ductal carcinoma. Of those who developed a second malignancy, the only patient who received XRT, was a patient who developed infiltrating ductal carcinoma in the contralateral breast 7 years after completing XRT. Address correspondence and reprint requests to: Gary Y. Yang, MD, Department of Radiation Medicine, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, NY 14263, or e-mail: Gary.yang@roswellpark.org.

The effect of smoking history on response and survival outcomes patients with in esophageal cancer treated with neoadjuvant concurrent chemoradiotherapy followed by surgery.

e14601 Background: There is limited information on the impact of current or former smoking status on survival outcomes in esophageal cancer patients treated with trimodality therapy. METHODS Patients with esophageal carcinoma who completed neoadjuvant concurrent chemoradiotherapy and underwent surgical resection between October 2002 and April 2010 at Roswell Park Cancer Institute were analyzed. Smoking history was abstracted from consultation notes at initial presentation. Survival was compared between patients with any self-reported history of smoking (current or former smokers) and patients who denied any prior history of smoking (never smokers). Follow up was calculated from the date of diagnosis to the date of death or last follow up. Unknown disease status was categorized as a recurrence. Unpaired t-tests were used for statistical comparisons. RESULTS A total of 115 patients were analyzed, of whom 11% were female and 77% of patients reported a current or former history of smoking. There was no difference in histology, mean radiotherapy dose delivered, chemoradiotherapy completion time, pathologic complete response rates, or total follow up time between groups. Never smokers had a much higher proportion of women as compared with current or former smokers (30.8% vs. 5.6%, p=0.0003). With a median follow-up time of 28 months, there was no difference in disease recurrence, disease specific mortality, or overall survival by self-reported smoking status (current or former vs. never smokers). CONCLUSIONS In esophageal cancer patients receiving neoadjuvant concurrent chemoradiotherapy followed by surgery, data suggest that a history of current or former smoking has no impact on pathologic complete response, recurrence, or survival. Analyses may be confounded by a higher proportion of women in the never smoking population.