Rahul R. Parikh

Ductal Carcinoma In Situ With Microinvasion: Prognostic Implications, Long-Term Outcomes, and Role of Axillary Evaluation

PURPOSE To compare the clinical-pathologic features and long-term outcomes for women with ductal carcinoma in situ (DCIS) vs. DCIS with microinvasion (DCISM) treated with breast conservation therapy (BCT), to assess the impact of microinvasion. PATIENTS AND METHODS A total of 393 patients with DCIS/DCISM from our database were analyzed to assess differences in clinical-pathologic features and outcomes for the two cohorts. RESULTS The median follow-up was 8.94 years, and the mean age was 55.8 years for the entire group. The DCISM cohort was comprised of 72 of 393 patients (18.3%). Surgical evaluation of the axilla was performed in 58.3% (n = 42) of DCISM vs. 18.1% (n = 58) of DCIS, with only 1 of 42 DCISM (2.3%) vs. 0 of 58 DCIS with axillary metastasis. Surgical axillary evaluation was not an independent predictor of local-regional relapse (LRR), distant relapse-free survival (DRFS), or overall survival (OS) in Cox proportional hazards analysis (p > 0.05). For the DCIS vs. DCISM groups, respectively, the 10-year breast relapse-free survival was 89.0% vs. 90.7% (p = 0.36), DRFS was 98.5% vs. 97.9% (p = 0.78), and OS was 93.2% vs. 95.7% (p = 0.95). The presence of microinvasion did not correlate with LRR, age, presentation, race, family history, margin status, and use of adjuvant hormonal therapy (all p > 0.05). In univariate analysis, pathology (DCIS vs. DCISM) was not an independent predictor of LRR (hazard ratio [HR], 1.58; 95% confidence interval [CI], 0.58-4.30; p = 0.36), DRFS (HR, 0.72; 95% CI, 0.07-6.95; p = 0.77), or OS (HR, 1.03; 95% CI, 0.28-3.82; p = 0.95). CONCLUSIONS Our data imply that the natural history of DCISM closely resembles that of DCIS, with a low incidence of local-regional and distant failures. On the basis of our large dataset, the incidence of axillary metastasis in DCISM appears to be small and not appear to correlate to outcomes, and thus, microinvasion alone should not be the sole criterion for more aggressive treatment.

Prognostic significance of IGF-1R expression in patients treated with breast-conserving surgery and radiation therapy

BACKGROUND Insulin-like growth factor (IGF) receptor is a key receptor in apoptotic protection, cell adhesion, longevity, and transformation into a cancerous cell and can induce malignant changes in the presence of the IGF ligand. Over-expression of IGF-1R has been associated with resistance to radiation. Inhibitors of IGF-1R have been shown to enhance tumor radiation sensitivity and amplify radiation therapy-induced apoptosis. The purpose of this study is to evaluate the prognostic significance of IGF-1R expression in patients with breast cancer treated with breast conserving therapy. MATERIALS AND METHODS Paraffin specimens from 345 women with early stage breast cancer treated with BCT were constructed into tissue microarrays and stained for IGF-1R, COX-2 and p53. The molecular profiles were correlated with clinical-pathologic factors, overall, local, and distant relapse-free survival. The association between IGF-1R, other co-variables, and outcome was assessed. RESULTS IGF-1R over-expression was identified in 197 cases (57%). IGF-1R over-expression was found to be correlated with African-American race (p=0.0233), p53 status (p=0.0082) and COX-2 expression (p<0.0001). While IGF-1R over-expression was associated with lower overall survival (p=0.0224) in node-negative patients, there was no impact of IGF-1R expression on local control. CONCLUSIONS In node-negative patients, patients with high levels of IGF-1R were found to have a significant reduction in overall survival, but no apparent effect on local control. Given the limited published data on IGF-1R in early stage, conservatively treated patients, further studies investigating IGF-1R expression in this cohort are necessary.

Disparities in survival by insurance status in patients with Hodgkin lymphoma

The association between insurance status and outcomes has not been well established for patients with Hodgkin lymphoma (HL). The purpose of this study was to examine the disparities in overall survival (OS) by insurance status in a large cohort of patients with HL.

Clinicopathologic Significance of Excision Repair Cross-Complementation 1 Expression in Patients Treated With Breast-Conserving Surgery and Radiation Therapy

PURPOSE The excision repair cross-complementation 1 (ERCC1) enzyme plays a rate-limiting role in the nucleotide excision repair pathway and is associated with resistance to platinum-based chemotherapy in cancers of the head and neck and the lung. The purpose of this study was to evaluate the clinicopathologic and prognostic significance of ERCC1 expression in a cohort of early-stage breast cancer patients treated with breast conservation therapy. METHODS AND MATERIALS Paraffin specimens from 504 women with early-stage breast cancer treated with breast conservation therapy were constructed into tissue microarrays. The array was stained for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) and ERCC1. This was then correlated with clinicopathologic factors and outcomes data. RESULTS ERCC-1 expression was evaluable in 366 cases (72%). In this group, 32% and 38% of patients received adjuvant chemotherapy and hormonal therapy, respectively. Increased ERCC-1 expression was found to be correlated with ER positivity (p < 0.005), lower T stage (p < 0.017), nodal negativity (p < 0.013), age >50 (p < 0.006), reduced use of adjuvant chemotherapy (p < 0.02), and increased use of adjuvant hormonal therapy (p < 0.004). ERCC1 expression did not correlate with locoregional recurrence-free survival, distant metastasis-free survival, cause-specific survival, or overall survival. In patients who were both ERCC1-negative and -positive, the use of chemotherapy predicted for worse distant metastasis-free survival (p = 0.05 and p = 0.07, respectively) but not cause-specific survival or overall survival. CONCLUSIONS Although ERCC1 expression did not predict for outcome measures in this dataset, overexpression correlated with favorable prognostic factors such as ER positivity, lower T stage, nodal negativity, and age >50. To our knowledge, this is the first study investigating ERCC1 expression in patients receiving adjuvant radiation therapy for breast cancer.

BCCIP as a prognostic marker for radiotherapy of laryngeal cancer

BACKGROUND Recent studies have shown that BCCIP (BRCA2 and CDKN1A interacting protein) is essential for maintaining the transactivation activity of wild type p53. We analyzed the expression of BCCIP and p53 in a cohort of laryngeal cancer treated with radiotherapy and assessed whether BCCIP and p53, alone or in combination, would correlate with local control and overall survival. METHODS One hundred twenty-three patients treated between 1975 and 2000 for early stage (stages I and II) squamous cell carcinoma of the larynx were included in the study. Treatment consisted of radiation therapy (RT) with standard fields and fractionation to a median dose of 66Gy. Tissue was collected from pre-RT biopsies and constructed in a tissue microarray, and BCCIP expression and p53 expression were determined using immunohistochemistry. RESULTS Loss of expression of BCCIP in combination with normal p53 (negative p53 staining) was associated with local recurrence (RR 2.04; 95% CI 0.99-4.56, p=0.05) and poor overall survival (RR 2.09; 95% CI 1.21-4.00, p=0.008) compared to patients who did express BCCIP. Expression of BCCIP or p53 alone was not found to be independently associated with benefits in local control or overall survival. CONCLUSIONS This study provides clinical evidence that BCCIP contributes to outcomes in patients with laryngeal cancer treated with RT. This benefit may be a result of increased radiosensitivity in patients who have functional BCCIP and p53. These data may be used to identify sub-groups of laryngeal cancer patients who are more likely to be cured with radiotherapy.

Local Therapy Improves Overall Survival in Patients With Newly Diagnosed Metastatic Prostate Cancer

The role of local therapy, in the form of radiation therapy (RT) or radical prostatectomy(RP), and its association on outcomes is not well established in patients with metastatic prostate cancer.

Long-term outcomes and patterns of failure in orbital lymphoma treated with primary radiotherapy

Abstract The purpose of this study was to evaluate the long-term outcome and patterns of failure in patients treated with primary radiotherapy (RT) for orbital lymphoma (OL). Seventy-nine patients diagnosed with stage IE OL between 1995 and 2012 were included. Fifty-nine patients (75%) had mucosa-associated lymphoid tissue lymphoma and 20 patients (25%) had follicular lymphoma subtype. The median follow-up was 49.7 months. Major tumor sites were conjunctiva (29%), orbit (47%) and lacrimal gland (24%). After treatment to a median dose of 30.6 Gy, there were a total of no local, one contralateral orbital, two regional and two distant recurrences, all outside of the treatment fields. The 10-year local relapse-free, distant metastasis-free and overall survival rates were 100%, 94.2% and 98.2%, respectively. Definitive RT to 30 Gy was shown to be highly effective for indolent OL, and this study represents one of the largest single-institution studies using primary RT for stage IE OL.

Evidence-based Review on the Use of Proton Therapy in Lymphoma From the Particle Therapy Cooperative Group (PTCOG) Lymphoma Subcommittee

Evidence-based Review on the Use of Proton Therapy in Lymphoma From the Particle Therapy Cooperative Group (PTCOG) Lymphoma Subcommittee Yolanda D. Tseng, MD,* David J. Cutter, MD, DPhil, FRCR,y John P. Plastaras, MD, PhD,z Rahul R. Parikh, MD,x Oren Cahlon, MD,k Michael D. Chuong, MD,{ Katerina Dedeckova, MD, Mohammad K. Khan, MD, PhD,** Shinn-Yn Lin, MD,yy Lisa A. McGee, MD,zz Eric Yi-Liang Shen, MD,yy Stephanie A. Terezakis, MD,xx ShahedN. Badiyan,MD,kk YouliaM. Kirova,MD,{{ Richard T. Hoppe,MD, Nancy P. Mendenhall, MD,***,yyy Mark Pankuch, PhD,zzz Stella Flampouri, PhD,***,yyy Umberto Ricardi, MD,xxx and Bradford S. Hoppe, MD, MPH***,yyy

Linear accelerator-based flattening-filter-free stereotactic radiosurgery for trigeminal neuralgia: Feasibility and patient-reported outcomes.

PURPOSE The purpose of this study was to assess the safety and outcomes of the clinical use of LINAC (linear accelerator)-based flattening-filter-free beams for delivering ablative stereotactic radiosurgery (SRS) for trigeminal neuralgia (TN). METHODS AND MATERIALS Thirty-six consecutive patients (34 unique patients) followed up by a single neurosurgeon and diagnosed with medically refractory unilateral TN were treated with SRS. There were 14 left-sided cases (41%) and 20 right-sided cases (59%). Twenty-eight of the patients (82%) had type 1 TN, and 6 (18%) had type 2 TN. Previous treatments were as follows: 10 patients (29%) had SRS to the ipsilateral TN (8 with Gamma Knife, 2 with LINAC), 4 (12%) had percutaneous rhizotomy, and 3 (9%) had microvascular decompression. A median prescription dose of 75 Gy (range, 70-80 Gy), prescribed to the 100% isodose line, was delivered in a single fraction. Before treatment delivery, image guidance verified stereotactic frame placement, head position, and final isocenter. The volume of brainstem receiving ≥10 Gy was <0.5 cm(3). At each visit, patients prospectively reported outcomes using the Barrow Neurological Institute (BNI) pain scale. RESULTS With a median follow-up of 3.1 months (range, 0.6-24.3; mean, 5.5 months), no patient experienced grade 1+ toxicities. There were no new episodes of dysesthesia, hypoesthesia, or long-term complications related to SRS. Median baseline (pre-SRS) BNI score was 5.0 (mean, 4.7). Clinical assessment at first follow-up (median, 1 month) demonstrated a median BNI score of 3.0 (mean, 3.1). When stratified by TN subtype, both type 1 and type 2 TN patients had a median BNI score of 3.0 at first follow-up. Thirty patients (88.2%) achieved a reduction in their BNI at their first follow-up, and 5 patients (15%) achieved a score <3, which represents medication-free pain relief. The median BNI at second follow-up (average, 6.3 months) was 2.5. CONCLUSIONS We report our experience with modern LINAC-based SRS using flattening-filter-free beams for TN. This treatment appears to be a safe and effective technique, although longer follow-up is needed to confirm durability. This modality may prove to be a viable treatment alternative for TN.

Impact of delays in definitive treatment on overall survival: a National Cancer Database study of patients with Hodgkin lymphoma.

Abstract The purpose of this large observational study was to examine outcomes in patients with Hodgkin lymphoma (HL) by timing to definitive chemotherapy (TTC) using standard and propensity score (PS)-adjusted Cox proportional hazards models. From 1998–2011, 56,457 patients with stage I–IV HL were studied, with a median follow-up of 6.0 years (median age = 39). Median TTC was 26 days from diagnosis. The cohort of “early” (<60 days from diagnosis) TTC patients included 45,307 (80.3%) patients and “late” (≥60 days) TTC was 11,150 (19.7%). Patients were more likely to experience early TTC if they were of a younger age, at an advanced stage, with “B” symptoms, favorably insured, favorable socioeconomic status, and treated at comprehensive cancer center (all p < 0.05). Ten-year overall survival for patients with early TTC was 73.2% vs. 70.0% for those with late TTC (HR = 0.87; 95%CI, 0.83–0.92, p < 0.0001). After PS-matching for co-variates, early TTC was not associated with overall survival (HR = 0.96; 95%CI, 0.85–1.08, p = 0.51). This represents the only study to evaluate overall survival by time to definitive treatment for HL