Sloan-Kettering Cancer Center Experience Research Articles

Etoposide and cisplatin (EP) for metastatic good-risk germ cell tumors (GCTs): The Memorial Sloan-Kettering Cancer Center (MSKCC) experience in 944 patients (pts).

4550Background: Standard of care for pts with metastatic, good-risk GCTs consists of either 3 cycles of bleomycin, etoposide, and cisplatin (BEPx3) or 4 cycles of EP (EPx4). EPx4 avoids both pulmon...

Medication-related osteonecrosis of the jaw: An update on the memorial sloan kettering cancer center experience and the role of premedication dental evaluation in prevention

The aim of this study was to investigate the relationship between type of antiresorptive medication and medication-related osteonecrosis of the jaw (MRONJ) onset and the role of premedication dental evaluation (PMDE) in the prevention of MRONJ. Our database of patients with MRONJ was reviewed. The Kruskal-Wallis test was used to analyze the onset dose of the 3 frequent medication types associated with MRONJ. To evaluate the role of PMDE in the prevention of MRONJ, all patients on antiresorptive and/or antiangiogenic medications seen in the Dental Service of Memorial Sloan Kettering Cancer Center during a 10-year period were subclassified into 2 groups. Group I comprised patients seen for PMDE before the commencement of A/A and group II patients seen after prior exposure to antiresorptive and/or antiangiogenic medications. Fischer's exact test was used to compare the incidence of MRONJ in both groups. Patients on denosumab developed MRONJ earlier compared with zoledronate and pamidronate (P = .003). Group I had a significantly reduced incidence of MRONJ (0.9%) compared with group II (10.5%) (P < .0001). Dentoalveolar trauma as a precipitating factor between groups I and II was not statistically significant. Denosumab was associated with an earlier occurrence of MRONJ compared with zoledronate and pamidronate. The role of PMDE may be an effective preventive strategy in reducing the incidence of MRONJ.

Bevacizumab (Bev) for treatment of recurrent serous borderline (SB) or low-grade serous (LGS) ovarian cancer: A retrospective review of the Memorial Sloan-Kettering Cancer Center (MSKCC) experience.

5545 Background: LGS ovarian cancer is a rare subtype of ovarian cancer, accounting for 10% of ovarian cancer cases. Patients typically present at an early age, exhibit a protracted clinical course, and have response rates to chemotherapy of &lt; 4%. Limited clinical data suggests that bev may have activity in this disease. The objective of this study was to determine the response rate to treatment with bev in patients with SB or LGS ovarian cancer treated at MSKCC. Methods: Following IRB approval, all patients with a diagnosis of SB or LGS ovarian or primary peritoneal cancer treated with ≥ 1 dose of bev for persistent or recurrent disease were identified. 17 patients were treated at MSKCC between July 2005 and June 2012. Diagnosis was confirmed by a gynecologic pathologist. All imaging was independently reviewed by the study radiologist and response was determined by RECIST 1.1 criteria. Results: 17 patients, 10 with LGS ovarian cancer, 3 with LGS primary peritoneal cancer, and 4 with SB disease were included in the analysis. The mean number of prior therapies was 3.4 (range: 1-9, median: 2). Two patients were treated with bev alone, the remainder (15) received bev in combination with paclitaxel (Pac, 6), topotecan (1), pemetrexed (1), oral cyclophosphamide (3), gemcitabine (Gem, 2), Gem and carboplatin (Carbo) (1), or Pac and Carbo (1) .Two patients were not evaluable for response due to termination of treatment prior to first radiographic assessment. The median duration of bev treatment was 23 weeks (mean: 32.2; range 6-79.4). Conclusions: This data suggests that the addition of bev to cytotoxic chemotherapy may produce dramatically higher response rates than chemotherapy alone in patients with SB and LGS ovarian cancer. A prospective study of bev for treatment of this chemotherapy resistant disease is warranted. [Table: see text]

Association between skin toxicities and treatment outcomes in patients with pancreatic cancer (PC) receiving erlotinib (E): Memorial Sloan-Kettering Cancer Center (MSKCC) experience.

294 Background: Rash is a common adverse event of E, an epidermal growth factor receptor (EGFR) inhibitor approved for advanced PC. Clinical trial results have shown that E-related rash grade 2 or higher is associated with a survival benefit in PC. We examined the correlation between all grades of rash and overall survival (OS) in PC patients receiving E at MSKCC. Methods: This was a retrospective single-institution study that included a review of all PC patients treated with E between March 1st 2005 and December 15th 2009 at MSKCC. The association of development of rash on OS was examined using a Cox proportional hazards model using development of rash as a time dependent covariate. The associations were examined univariately and after adjusting for gender, race, smoking history, prior lines of treatment for metastatic disease, and chemotherapy. An intervention was defined as a dose change, interruption, discontinuation or medical intervention for rash. Results: N=193 constituted the cohort of analysis. The median age was 64; 116 (60%) were male and 162 (84%) were Caucasian. Most patients (N=111, 58%) did not receive any prior medical treatment for pancreatic cancer. Skin rash occurred in 113 (59%) of patients. The median OS was 6.7 months (95% confidence interval, 5.7-7.9 months). In a univariate analysis, rash was protective compared to no skin rash (Grade 1 HR 0.71; 95% CI 0.50-1.00, Grade 2+ HR 0.57; 95% CI 0.40-0.82; P=0.007). In the multivariate model, rash appeared to have a protective effect on survival, but this was not statistically significant (Grade 1 HR 0.69; 95% CI 0.49-0.97, Grade 2+ HR 0.78; 95% CI 0.48-1.27). Non-medical interventions for rash included dose adjustment (5%), dose interruption (6%) and dose discontinuation (9%). 33 (29%) patients received medical intervention for rash. Conclusions: Our findings suggest that grade 1 or higher E-related rash may be a surrogate for survival. Appropriate symptom interventions are recommended to enhance patient comfort and avoid discontinuation of treatment.

Risk of breast cancer (BC) after BRCA-mutation associated ovarian cancer (BRCA-OC): Memorial Sloan-Kettering Cancer Center (MSKCC) experience.

1518 Background: Women (W) with BRCA mutation-associated BC are at significant risk for metachronous OC, ranging from 0.8-1.5% per year. The risk of BC after a diagnosis (Dx) of BRCA-OC is unknown....

Intensity-Modulated Radiotherapy in the Treatment of Oropharyngeal Cancer: An Update of the Memorial Sloan-Kettering Cancer Center Experience

To update the Memorial Sloan-Kettering Cancer Center's experience with intensity-modulated radiotherapy (IMRT) in the treatment of oropharyngeal cancer (OPC). Between September 1998 and April 2009, 442 patients with histologically confirmed OPC underwent IMRT at our center. There were 379 men and 63 women with a median age of 57 years (range, 27-91). The disease was Stage I in 2%, Stage II in 4%, Stage III in 21%, and Stage IV in 73% of patients. The primary tumor subsite was tonsil in 50%, base of tongue in 46%, pharyngeal wall in 3%, and soft palate in 2%. The median prescription dose to the planning target volume of the gross tumor was 70 Gy for definitive (n = 412) cases and 66 Gy for postoperative cases (n = 30). A total 404 patients (91%) received chemotherapy, including 389 (88%) who received concurrent chemotherapy, the majority of which was platinum-based. Median follow-up among surviving patients was 36.8 months (range, 3-135). The 3-year cumulative incidence of local failure, regional failure, and distant metastasis was 5.4%, 5.6%, and 12.5%, respectively. The 3-year OS rate was 84.9%. The incidence of late dysphagia and late xerostomia ≥Grade 2 was 11% and 29%, respectively. Our results confirm the feasibility of IMRT in achieving excellent locoregional control and low rates of xerostomia. According to our knowledge, this study is the largest report of patients treated with IMRT for OPC.

Patterns of care and outcomes in patients with intracranial hemangiopericytomas: The Memorial Sloan-Kettering Cancer Center (MSKCC) experience

e13011 Background: Intracranial hemangiopericytomas are rare primary brain tumors with a tendency to metastasize. Available literature is restricted to small series of patients, and little is known regarding optimal clinical management and disease course, particularly in the targeted therapy era. Methods: Retrospective review of all patients with intracranial hemangiopericytoma seen at MSKCC from January 1, 1990 to December 31, 2008. Patients were included if histology was reviewed at MSKCC, and if clinical information was deemed sufficient for the analysis. Results: A total of 32 patients met inclusion criteria. The median age was 43 (range 24–68), median KPS was 80 (range 70–100), 17 were women. Disease was metastatic at presentation in only one patient. Initial treatment consisted of surgical resection in all patients (gross total resection: 14 patients, partial resection: 7, equivocal/unknown extent of surgery: 11). Adjuvant radiotherapy following surgery was given to 21 patients. The median progression-free survival was 65 months; median overall survival was 153 months and the 15-year survival was 48%. Treatment for recurrence included re-resection in 19 patients, additional radiotherapy in 17, and chemotherapy in 10. Regimens used included cytotoxic chemotherapy (6 patients) and targeted therapy (sorafenib: 3 patients; sunitinib: 3; imatinib: 2; erlotinib: 1; sirolimus: 1; bevacizumab: 1). Stable disease was the best observed response to these agents. Metastatic sites throughout disease course included lungs in 7 patients, bone in 10, liver in 3 and chest wall in 2. Immunohistochemistry and molecular analyses are ongoing and updated results will be presented. Conclusions: Hemangiopericytomas can be associated with late recurrences, even in patients completely resected and irradiated. Salvage treatment with surgery and radiotherapy seems effective, although the efficacy of chemotherapy remains to be determined. Given the slow growth rates, the meaning of stable disease while on chemotherapy is uncertain. Several patients in this series received agents targeting PDGFR or VGFR pathways, but such strategies need to be investigated further. No significant financial relationships to disclose.

Treatment outcome and survival for patients (pts) with sarcomatoid-variant metastatic renal cell carcinoma (RCC): Memorial Sloan-Kettering Cancer Center (MSKCC) experience

e16017 Background: Sarcomatoid-variant represents a spindle cell phenotype of RCC that can be present in any subtype, usually showing aggressive biological behavior. MSKCC experience was studied to provide data on outcome and survival to systemic therapy for metastatic, sarcomatoid-variant RCC. Methods: Clinical features, treatment outcome and survival were reviewed in 63 pts with sarcomatoid-variant metastatic RCC from a database of 650 pts treated at MSKCC with systemic therapy (cytokines, anti-angiogenesis targeted therapy and chemotherapy). Response to therapy, progression-free survival (PFS), and overall survival (OS) was determined for pts based on their first treatment at MSKCC. The percentage of sarcomatoid component in the tumors was assessed. Results: Histology subtypes with sarcomatoid-variant among the 63 pts included 46 clear cell, 5 papillary, 5 chromophobe, 1 collecting duct, and 6 unclassified. 60 pts had prior nephrectomy. MSKCC risk group distribution was 37% good risk, 59% intermediate risk, and 5% poor risk. 34 pts received targeted therapy (29 sunitinib, 3 sorafenib, 2 temsirolimus), 20 pts received cytokine therapy (19 interferon, 1 interleukin) and 9 received other therapies. 5/63 pts achieved an objective response: 1/19 to interferon and 4/29 to sunitinib. In 63 pts, median PFS was 3 months (95% CI 2–4) and median OS was 10 months (95% CI 8–14). Differences in PFS were observed based on therapy (sunitinib vs. all other) and histology (clear cell vs. non-clear cell). The median PFS for sunitinib therapy was 4.4 months (95% CI 2.2–6.7) versus 2 months (95% CI 1.7–2.7) for all other therapies (p = 0.02); and 3 months (95% CI 2.3–4.5) for clear cell versus 1.6 months (95% CI 1.0–2.1) for non-clear cell histology (p = 0.007). In a subset (n = 31) with available specimen, the median % sarcomatoid content was 20% (range 2%-100%). No difference in PFS or OS was observed according to % sarcomatoid content. Conclusions: Metastatic sarcomatoid-variant RCC is associated with a poor prognosis. Sunitinib resulted in a modest response rate and longer PFS versus other therapies. Studies to assess outcome, characterize tumor biology, and develop novel treatment strategies are warranted. [Table: see text]

Postoperative intensity‐modulated radiation therapy for cancers of the paranasal sinuses, nasal cavity, and lacrimal glands: Technique, early outcomes, and toxicity

Our aim was to review Memorial Sloan-Kettering Cancer Center's experience with postoperative intensity-modulated radiotherapy (IMRT) for paranasal sinus, nasal cavity, and lacrimal gland cancer and report dosimetric measures, toxicity, and outcomes. Between September 2000 and June 2006, 37 patients with paranasal sinus, nasal cavity, or lacrimal gland cancer underwent postoperative IMRT. Median values were as follows: prescription dose, 60 Gy (range, 50-70); PTV(D95), 99% (range, 79-101%); optic nerve Dmax, 53 Gy (range, 2-54); optic chiasm Dmax, 51Gy (range, 2-55). Acute and late toxicities were scored by Radiation Therapy Oncology Group morbidity criteria. Median follow-up was 28 months. Two-year local progression-free and overall survivals were 75% and 80%. No early- or late-grade 3/4 radiation-induced ophthalmologic toxicity occurred. Preliminary results show that adjuvant IMRT in these patients is feasible, allowed for excellent planning target volume (PTV) coverage, and minimized dose delivered to optic structures. Longer follow-up is warranted to assess the extent of late effects and outcomes.

Small cell carcinoma of the esophagus: Review of the Memorial Sloan-Kettering Cancer Center (MSKCC) experience

4631 Background: Esophageal small cell carcinoma (ESC) is rare and accounts for &lt;1% of all esophageal cancers. It is treated like pulmonary SC but the optimal approach of surgery, chemotherapy or radiotherapy is unknown. Prior series (Chest 107:179, Cancer 88:262) indicate a poor median overall survival (OS) of 7–12 months (mos), rare long-term (LT) survival and the need for surgery as part of curative therapy. Methods: We reviewed records of patients (pts) with ESC treated from 1980 to 2005. All pathology was reviewed at MSKCC. Results: 24 pts were identified, with records available for 21. 86% male, 14% female, median age 60, 67% smokers. 81% had pure SC histology, with 85% of tumors in the lower esophagus or gastroesophageal junction. 13/21 (62%) had limited disease (LD) by VALSG criteria. For extensive disease (ED), liver (63%) was most common metastatic site (mets). Treatment for LD was: chemotherapy (chemo) only (3 pts, 23%), surgery only (1 pt, 8%), surgery and adjuvant chemo (3 pts) and chemoradiation (CRT) without surgery (6 pts, 46%). The most common chemo given was cisplatin/carboplatin and etoposide (81%). Pts with ED received chemo alone. Overall median survival was 19.8 mos (range, 1.5 mos to 11.2+ years (yrs)); for LD Pts, 22.3 mos (range, 6 mos to 11.2+ yrs); for ED Pts, 10.9 mos (range, 1.5 mos to 2.2 yrs). At median follow-up of 32 mos, 5 pts are alive (4 without disease (NED) and 1 with disease); 2 pts are alive &gt;5 yrs. 4 originally had LD and 3 of 4 received CRT only without surgery. None received whole brain radiation (WBXRT). 1 LD pt treated with surgery and adjuvant chemo recurred after 4 yrs, was salvaged with CRT and is NED 11.2 yrs after diagnosis. Of 18 pts with progression, 10 (56%) had new mets. Most common site was liver (4 pts) and only 1 pt had brain mets. Of 6 pts with LD who received CRT only, 3 recurred (1 local and 2 distant). Of 4 pts with LD who underwent surgery, all recurred (1 local, 3 distant). Conclusions: Pts with ESC with LD who received CRT without surgery can have LT survival. The role of surgery remains unclear. LT survival for 1 pt who underwent salvage CRT for recurrence after surgery argues for aggressive therapy for recurrence. Unlike pulmonary SC, brain mets are uncommon and WBXRT may not be needed for LT survival. No significant financial relationships to disclose.

Treatment outcome and incidence for late relapse of germ cell tumor (GCT) patients (pts): The memorial Sloan-Kettering Cancer Center (MSKCC) experience

4522 Background: Late relapse GCT occurs > 2 years after initial chemotherapy and is associated with a poor prognosis (JCO 13:1170). The MSKCC experience with late relapse GCT was examined from two...

Intensity-modulated radiation therapy for the treatment of oropharyngeal carcinoma: The Memorial Sloan-Kettering Cancer Center experience

To review the Memorial Sloan-Kettering Cancer Center's experience in using intensity-modulated radiation therapy (IMRT) for the treatment of oropharyngeal cancer. Between September 1998 and June 2004, 50 patients with histologically confirmed cancer of the oropharynx underwent IMRT at our institution. There were 40 men and 10 women with a median age of 56 years (range, 28-78 years). The disease was Stage I in 1 patient (2%), Stage II in 3 patients (6%), Stage III in 7 (14%), and Stage IV in 39 (78%). Forty-eight patients (96%) received definitive treatment, and 2 (4%) were treated in the postoperative adjuvant setting. Concurrent chemotherapy was used in 43 patients (86%). Patients were treated using three different IMRT approaches: 76% dose painting, 18% concomitant boost with IMRT in both am and pm deliveries, and 6% concomitant boost with IMRT only in pm delivery. Regardless of the approach, the average prescription dose to the gross tumor planning target volume was 70 Gy, while the average dose delivered to the subclinical volume was 59.4 Gy in the dose painting group and 54 Gy in the concomitant boost group. Percutaneous endoscopic gastrostomy feeding tubes (PEGs) were placed before the beginning of treatment in 84% of the patients. Acute and late toxicity were graded according to the Radiation Therapy Oncology Group (RTOG) radiation morbidity scoring criteria. Toxicity was also evaluated using subjective criteria such as the presence of esophageal stricture, and the need for PEG usage. The local progression-free, regional progression-free, and distant metastases-free rates, and overall survival were calculated using the Kaplan-Meier method. Three patients had persistent locoregional disease after treatment. The 2-year estimates of local progression-free, regional progression-free, distant metastases-free, and overall survival were 98%, 88%, 84%, and 98%, respectively. The worst acute mucositis experienced was Grade 1 in 4 patients (8%), Grade 2 in 27 (54%), and Grade 3 in 19 (38%). Xerostomia decreased with increasing time interval from the end of radiotherapy, and among the patients with at least 9 months of follow-up there was 67% Grade 0-1 and 33% Grade 2 toxicity. Of the 42 patients who required upfront PEG placement, 6 were still using PEG for nutrition at the time of this analysis. Three patients had cervical esophageal strictures, and of these, 1 was still PEG dependent 1 year after treatment. Two of these patients were treated with the IMRT concomitant boost am and pm approach, whereas the other was treated with the dose painting technique. Intensity-modulated radiotherapy achieved encouraging local control rates in patients with oropharyngeal carcinoma. Treatment toxicity was acceptable even in the setting of concurrent chemotherapy. Long-term follow-up is needed to confirm these preliminary findings.

Etoposide and cisplatin (EP) chemotherapy for good risk germ cell tumors (GCT): The Memorial Sloan-Kettering Cancer Center (MSKCC) experience

4533 Background: Phase 3 trials at MSKCC showed 4 cycles of EP to be effective and tolerable treatment for good risk advanced GCTs (JCO 1997;15:2553). Additional patients (pts) have been treated and follow-up (f/u) updated to detect late relapses. Methods: 379 pts with good risk GCT received EP from 11/82–12/02 on 4 protocols. MSKCC criteria (Cancer 1991;67:28) were used to assign risk status prospectively until 8/1994. Thereafter, the International Germ Cell Consensus Classification Group (IGCCCG) criteria were used. All pts were retrospectively classified according to IGCCCG criteria. EP consisted of 4 cycles of etoposide 100 mg/m2 and cisplatin 20 mg/m2 days 1–5 every 21 days. Results: 295/379 (78%) had nonseminoma; 84 (22%) had seminoma. Primary site was testis-365 (96%), retroperitoneum-8 (2%), mediastinum-6 (2%). By IGCCCG criteria, 291 (77%) were good risk, 75 (20%) intermediate risk and 13 (3%) poor risk. Of 291 IGCCCG good risk pts, 284 achieved a CR [98%; 273 to chemotherapy (c) and 11 to chemo+...

Etoposide and cisplatin (EP) chemotherapy for good risk germ cell tumors (GCT): The Memorial Sloan-Kettering Cancer Center (MSKCC) experience

Etoposide and cisplatin (EP) chemotherapy for good risk germ cell tumors (GCT): The Memorial Sloan-Kettering Cancer Center (MSKCC) experience