Richard J. Bleicher

Radiofrequency Ablation in 447 Complex Unresectable Liver Tumors: Lessons Learned

Background: Radiofrequency ablation (RFA) is a promising technique for unresectable hepatic malignancies. We reviewed our RFA experience to identify variables affecting local recurrence.Methods: Patients undergoing RFA between 1997 and 2001 were reviewed for demographics, tumor size, pathology, diagnosis, recurrence, procedures, survival, and complications.Results: The 447 unresectable liver tumors were ablated in 198 procedures. The 153 patients averaged 61.9 years of age and 1.25 RFA procedures per patient. Follow-up averaged 11 months. Serial ablations were performed in 28 patients, 8 of whom are without evidence of disease. Tumors were most commonly carcinomas of colorectal, hepatocellular, breast, and melanoma histologies. Colorectal carcinomas and hepatomas individually recurred more frequently than all other tumor types combined in univariate analyses (P = .009 and P = .008, respectively). Patients with multiple tumors ablated recurred significantly more frequently (P = .001). Size was also significant in univariate and multivariate analyses (P = .0032 and &<.0001, respectively). Eighteen patients experienced 36 complications.Conclusions: Size has the highest correlation with local recurrence, but multiple tumors and pathology may also predict local recurrence risk. Large, complex lesions can be safely serially ablated, but because of morbidity and recurrence, RFA should not replace resection as the primary treatment of resectable liver tumors.

Association of Routine Pretreatment Magnetic Resonance Imaging with Time to Surgery, Mastectomy Rate, and Margin Status

BACKGROUND The benefit of breast MRI for newly diagnosed breast cancer patients is uncertain. This study characterizes those receiving MRI versus those who did not, and reports on their short-term surgical outcomes, including time to operation, margin status, and mastectomy rate. STUDY DESIGN All patients seen in a multidisciplinary breast cancer clinic from July 2004 to December 2006 were retrospectively reviewed. Patients were evaluated by a radiologist, a pathologist, and surgical, radiation, and medical oncologists. RESULTS Among 577 patients, 130 had pretreatment MRIs. MRI use increased from 2004 (referent, 13%) versus 2005 (24%, p=0.014) and 2006 (27%, p=0.002). Patients having MRIs were younger (52.5 versus 59.0 years, p < 0.001), but its use was not associated with preoperative chemotherapy, family history of breast or ovarian cancer, presentation, or tumor features. MRI was associated with a 22.4-day delay in pretreatment evaluation (p=0.011). Breast conserving therapy (BCT) was attempted in 320 of 419 patients with complete surgical data. The odds ratio for mastectomy, controlling for T size and stage, was 1.80 after MRI versus no MRI (p=0.024). Patients having MRIs did not have fewer positive margins at lumpectomy (21.6% MRI versus 13.8% no MRI, p=0.20), or conversions from BCT to mastectomy (9.8% MRI versus 5.9% no MRI, p=0.35). CONCLUSIONS Breast MRI use was not confined to any particular patient group. MRI use was not associated with improved margin status or BCT attempts, but was associated with a treatment delay and increased mastectomy rate. Without evidence of improved oncologic outcomes as a result, our study does not support the routine use of MRI to select patients or facilitate the performance of BCT.

Role of Sentinel Lymphadenectomy in Thin Invasive Cutaneous Melanomas

PURPOSE Regional lymph node status is the strongest prognostic determinant in early-stage melanoma. Lymphatic mapping and sentinel lymphadenectomy (LM/SL) is standard to stage regional nodes because it is accurate and minimally morbid, yet its role for thin (<or= 1.5 mm) primary melanomas is unknown. PATIENTS AND METHODS Our melanoma database of more than 10,000 patients was reviewed for patients with melanomas <or= 1.50 mm thick who underwent LM/SL. All had lymphoscintigrams and LM/SL via dye alone or with radiopharmaceutical. Patients with tumor-positive sentinel nodes (SNs) underwent completion dissections. RESULTS Five hundred twelve patients underwent LM/SL. Most were men (57%), and median age was 49 years. Most primary melanomas were on the torso (44%). Twenty-five patients (4.9%) had tumor-positive SNs. The thinnest lesion with a nodal metastasis was 0.35 mm. The SN-negative and SN-positive cohorts were equivalent by sex, but SN+ patients tended to be younger (P =.053), with significantly more SN metastases in those younger than 44 years (P =.005). No consistent pathology among SN-positive primary melanomas was found. Among those with 1.01- to 1.05-mm primaries, 7.1% were SN-positive. Among 272 patients with lesions <or= 1.00 mm, 2.9% had positive SNs and 1.7% with lesions <or= 0.75 mm had SN metastases. All 13 deaths were in SN-negative patients. Median follow-up durations in SN-positive and SN-negative patients were 25 and 45 months, respectively. CONCLUSION The high nodal positivity rate associated with primary melanomas 1.01 to 1.50 mm thick suggests that LM/SL is indicated in this group. Younger age may be correlated with nodal metastases in patients with lesions <or= 1.00 mm. Lesions <or= 0.75 mm have minimal metastatic potential, and therefore LM/SL is rarely indicated.

Prognostic implications of thick (≥4-mm) melanoma in the era of intraoperative lymphatic mapping and sentinel lymphadenectomy

BackgroundLymphatic mapping/sentinel lymphadenectomy (LM/SL) has become a routine part of our treatment algorithm for primary melanoma, yet its role in the management of thick (≥4-mm) lesions is unknown.MethodsOne hundred twenty-one patients with thick primaries underwent LM/SL at our institute. Survival curves were constructed from Kaplan-Meier estimates and analyzed by Cox proportional hazards methods.ResultsSixty-three percent of patients were men, median age 54 years. The primary tumor sites were trunk (46%), extremities (32%), and head and neck (21%). Primary thickness ranged from 4 to 15 mm (median, 6.0 mm). Forty-five percent of primary tumors were ulcerated. Thirty-five percent of patients had tumor-positive dissections. Median follow-up was 31 months. The overall 5-year survival was no different (P=.726) for ulcerated and nonulcerated lesions. There was no difference (P=.159) in overall survival after tumor-negative (60%±7%) and tumor-positive (50%±10%) dissections. The 5-year disease-free survival was significantly (P=.012) lower in patients with tumor-positive (34%±9%) than tumor-negative (47%±7%) dissections.ConclusionsAlthough LM/SL has become a popular technique for staging the regional lymph nodes in early-stage melanoma, our results suggest that sentinel node status is predictive of disease-free survival for thick primary tumors but is not yet reflective of overall survival. The role of LM/SL for patients with thick primary tumors is not clearly defined.

Time to Surgery and Breast Cancer Survival in the United States.

IMPORTANCE Time to surgery (TTS) is of concern to patients and clinicians, but controversy surrounds its effect on breast cancer survival. There remains little national data evaluating the association. OBJECTIVE To investigate the relationship between the time from diagnosis to breast cancer surgery and survival, using separate analyses of 2 of the largest cancer databases in the United States. DESIGN, SETTING, AND PARTICIPANTS Two independent population-based studies were conducted of prospectively collected national data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database and the National Cancer Database (NCDB). The SEER-Medicare cohort included Medicare patients older than 65 years, and the NCDB cohort included patients cared for at Commission on Cancer-accredited facilities throughout the United States. Each analysis assessed overall survival as a function of time between diagnosis and surgery by evaluating 5 intervals (≤30, 31-60, 61-90, 91-120, and 121-180 days) and disease-specific survival at 60-day intervals. All patients were diagnosed with noninflammatory, nonmetastatic, invasive breast cancer and underwent surgery as initial treatment. MAIN OUTCOMES AND MEASURES Overall and disease-specific survival as a function of time between diagnosis and surgery, after adjusting for patient, demographic, and tumor-related factors. RESULTS The SEER-Medicare cohort had 94 544 patients 66 years or older diagnosed between 1992 and 2009. With each interval of delay increase, overall survival was lower overall (hazard ratio [HR], 1.09; 95% CI, 1.06-1.13; P < .001), and in patients with stage I (HR, 1.13; 95% CI, 1.08-1.18; P < .001) and stage II disease (HR 1.06; 95% CI, 1.01-1.11; P = .01). Breast cancer-specific mortality increased with each 60-day interval (subdistribution hazard ratio [sHR], 1.26; 95% CI, 1.02-1.54; P = .03). The NCDB study evaluated 115 790 patients 18 years or older diagnosed between 2003 and 2005. The overall mortality HR was 1.10 (95% CI, 1.07-1.13; P < .001) for each increasing interval, significant in stages I (HR, 1.16; 95% CI, 1.12-1.21; P < .001) and II (HR, 1.09; 95% CI, 1.05-1.13; P < .001) only, after adjusting for demographic, tumor, and treatment factors. CONCLUSIONS AND RELEVANCE Greater TTS is associated with lower overall and disease-specific survival, and a shortened delay is associated with benefits comparable to some standard therapies. Although time is required for preoperative evaluation and consideration of options such as reconstruction, efforts to reduce TTS should be pursued when possible to enhance survival.

Preoperative Delays in the US Medicare Population With Breast Cancer

PURPOSE Although no specific delay threshold after diagnosis of breast cancer has been demonstrated to affect outcome, delays can cause anxiety, and surgical waiting time has been suggested as a quality measure. This study was performed to determine the interval from presentation to surgery in Medicare patients with nonmetastatic invasive breast cancer who did not receive neoadjuvant chemotherapy and factors associated with a longer time to surgery. METHODS Medicare claims linked to Surveillance, Epidemiology, and End Results data were reviewed for factors associated with delay between the first physician claim for a breast problem and first therapeutic surgery. RESULTS Between 1992 and 2005, 72,586 Medicare patients with breast cancer had a median interval (delay) between first physician visit and surgery of 29 days, increasing from 21 days in 1992 to 32 days in 2005. Women (29 days v 24 days for men; P < .001), younger patients (29 days; P < .001), blacks and Hispanics (each 37 days; P < .001), patients in the northeast (33 days; P < .001), and patients in large metropolitan areas (32 days; P < .001) had longer delays. Patients having breast conservation and mastectomies had adjusted median delays of 28 and 30 days, respectively, with simultaneous reconstruction adding 12 days. Preoperative components, including imaging modalities, biopsy type, and clinician visits, were also each associated with a specific additional delay. CONCLUSION Waiting times for breast cancer surgery have increased in Medicare patients, and measurable delays are associated with demographics and preoperative evaluation components. If such increases continue, periodic assessment may be required to rule out detrimental effects on outcomes.

Impact of the radiation boost on outcomes after breast-conserving surgery and radiation.

PURPOSE We examined the impact of radiation tumor bed boost parameters in early-stage breast cancer on local control and cosmetic outcomes. METHODS AND MATERIALS A total of 3,186 women underwent postlumpectomy whole-breast radiation with a tumor bed boost for Tis to T2 breast cancer from 1970 to 2008. Boost parameters analyzed included size, energy, dose, and technique. Endpoints were local control, cosmesis, and fibrosis. The Kaplan-Meier method was used to estimate actuarial incidence, and a Cox proportional hazard model was used to determine independent predictors of outcomes on multivariate analysis (MVA). The median follow-up was 78 months (range, 1-305 months). RESULTS The crude cosmetic results were excellent in 54%, good in 41%, and fair/poor in 5% of patients. The 10-year estimate of an excellent cosmesis was 66%. On MVA, independent predictors for excellent cosmesis were use of electron boost, lower electron energy, adjuvant systemic therapy, and whole-breast IMRT. Fibrosis was reported in 8.4% of patients. The actuarial incidence of fibrosis was 11% at 5 years and 17% at 10 years. On MVA, independent predictors of fibrosis were larger cup size and higher boost energy. The 10-year actuarial local failure was 6.3%. There was no significant difference in local control by boost method, cut-out size, dose, or energy. CONCLUSIONS Likelihood of excellent cosmesis or fibrosis are associated with boost technique, electron energy, and cup size. However, because of high local control and rare incidence of fair/poor cosmesis with a boost, the anatomy of the patient and tumor cavity should ultimately determine the necessary boost parameters.

Five-year Local Control in a Phase II Study of Hypofractionated Intensity Modulated Radiation Therapy With an Incorporated Boost for Early Stage Breast Cancer

PURPOSE Conventional radiation fractionation of 1.8-2 Gy per day for early stage breast cancer requires daily treatment for 6-7 weeks. We report the 5-year results of a phase II study of intensity modulated radiation therapy (IMRT), hypofractionation, and incorporated boost that shortened treatment time to 4 weeks. METHODS AND MATERIALS The study design was phase II with a planned accrual of 75 patients. Eligibility included patients aged≥18 years, Tis-T2, stage 0-II, and breast conservation. Photon IMRT and an incorporated boost was used, and the whole breast received 2.25 Gy per fraction for a total of 45 Gy, and the tumor bed received 2.8 Gy per fraction for a total of 56 Gy in 20 treatments over 4 weeks. Patients were followed every 6 months for 5 years. RESULTS Seventy-five patients were treated from December 2003 to November 2005. The median follow-up was 69 months. Median age was 52 years (range, 31-81). Median tumor size was 1.4 cm (range, 0.1-3.5). Eighty percent of tumors were node negative; 93% of patients had negative margins, and 7% of patients had close (>0 and <2 mm) margins; 76% of cancers were invasive ductal type: 15% were ductal carcinoma in situ, 5% were lobular, and 4% were other histology types. Twenty-nine percent of patients 29% had grade 3 carcinoma, and 20% of patients had extensive in situ carcinoma; 11% of patients received chemotherapy, 36% received endocrine therapy, 33% received both, and 20% received neither. There were 3 instances of local recurrence for a 5-year actuarial rate of 2.7%. CONCLUSIONS This 4-week course of hypofractionated radiation with incorporated boost was associated with excellent local control, comparable to historical results of 6-7 weeks of conventional whole-breast fractionation with sequential boost.

Young age is not associated with increased local recurrence for DCIS treated by breast-conserving surgery and radiation†

We report local recurrence (LR) after breast‐conserving surgery and radiation (BCS + RT) for ductal carcinoma in situ (DCIS) to determine outcomes for patients aged ≤40 years compared with older women.

Inflammatory cutaneous adverse effects of methylene blue dye injection for lymphatic mapping/sentinel lymphadenectomy

Methylene blue (MB) dye has been used for lymphatic mapping/sentinel lymphadenectomy (LM/SL) in staging of melanoma and breast cancer. It has been noted to cause skin necrosis, but its more mild adverse effects from intraparenchymal breast injections are not well characterized.