Local-regional Disease Research Articles

Contralateral axillary nodal involvement from invasive breast cancer

Metastatic breast cancer to the contralateral axilla (CAM) is defined as stage IV disease. We postulate that CAM represents an extension of local-regional disease rather than distant metastasis and may have a better outcome. A single-institution, retrospective review of breast cancer cases from January 2005 and May 2011 was performed to identify cases with CAM. Eligibility for the study included unilateral primary breast cancer at presentation with synchronous/metachronous documented CAM without a documented primary invasive breast cancer within the contralateral breast by surgery or MRI. Clinicopathologic data was recorded for these patients (pts). Thirteen pts were identified. 12/13 (92%) pts presented with a locally advanced breast tumor or an ipsilateral in-breast recurrence. 10/13 (77%) pts had documented dermal involvement of tumor either at initial presentation or local recurrence. CAM occurred synchronously with the initial primary tumor (5 pts, 38%), concomitant with a local recurrence (5 pts, 38%), metachronously with the initial tumor (1 pt, 8%), and metachronously with a local recurrence (2 pts, 15%). Three patients had other distant disease at presentation. Of the other 10 pts, seven developed distant disease with a mean follow up of 3.6 years (range 0.3–7.6 years). Three pts have no evidence of disease at a mean follow up of 5.8 years (range 1.5–8.2). CAM may have different prognostic implications than other distant metastases and may occur through dermal lymphatic spread. Further study is warranted on the prognosis and management of these challenging and rare cases.

The influence of FDG PET-CT on the detection of extrahepatic disease in patients being considered for resection of colorectal liver metastasis.

The aim of this study was to evaluate the influence of flurodeoxyglucose positron emission tomography computed tomography (FDG PET-CT), as an adjunct to conventional CT staging, in the detection of extrahepatic disease in patients with potentially resectable colorectal liver metastasis. Overall, 133 consecutive patients with colorectal liver metastases staged with CT and PET-CT referred to the East Lancashire regional hepatobiliary multidisciplinary team over a two-year period were included in this study. Abnormal findings on PET-CT were correlated with follow-up imaging and/or histology. All imaging was reviewed by specialist hepatobiliary radiologists for the presence/absence of extrahepatic disease. The influence of the PET-CT findings was categorised for each patient in relation to operability and other significant findings. PET-CT had a major impact on staging of extra hepatic disease in 20% of patients, in comparison with the initial CT. Six per cent of patients were upstaged from operable CT findings to inoperable findings on PET-CT because of the discovery of inoperable occult extrahepatic disease. Five per cent had operable local regional nodal disease detected on PET-CT. A further 3% had premalignant colorectal lesions detected on PET-CT. Six per cent of patients were downstaged from indeterminate or suspected inoperable CT findings to operable findings on PET-CT. The use of PET-CT in this setting may prevent futile operations, guide the resection of local regional nodal disease and downstage a number of patients thought to have extrahepatic disease on conventional imaging. This study has shown similar results to other recent studies and supports the use of PET-CT as a necessary staging modality in patients with potentially resectable colorectal liver metastases.

Abstract CS01-2: The role of radiation in the treatment of the axilla in the setting of neoadjuvant chemotherapy

Abstract There is considerable controversy regarding the appropriate surgical procedure and its timing for evaluating the status of the axillary nodes in the neoadjuvant setting. Sentinel lymph node (SLN) surgery following initial chemotherapy avoids an axillary dissection and its associated morbidity in clinical N0 patients who have pathologic negative SLN. SLN identification and false negative rates (FNR) have been acceptable in these women and axillary recurrence rates without radiation directed to the axilla are £1%. For clinical N1 disease, 2 recent studies (SENTINA, ACOSOG 1071) reported SLN identification rates of 80% and 91%, FNR of 12.8 and 14% and ypN0 rates of 52% and 40% respectively. The SLN was the only positive node(s) in 58% and 40% of the ypN1 patients. Several studies have evaluated the role of regional node (RN) irradiation in clinical N1 patients who are ypN0 following neoadjuvant chemotherapy and have found no improvement in local-regional disease free survival. RN failure rates are low as reported by the NSABP B18 and 27 trials in the absence of post mastectomy radiation or with breast only radiation. The question of RN radiation is being addressed by an NRG (NSABP-RTOG) randomized trial. For women with clinical N1 disease who remain ypN1, axillary radiation may substitute for axillary dissection. Axillary radiation has been shown in randomized trials to be equivalent to axillary dissection in the adjuvant setting for clinical N0 women (NSABP B04) including those with positive SLN (Dutch Mirror, IBCSG 23-01, AMAROS). The Alliance trial will address this question. The potential advantage of neoadjuvant chemotherapy is the ability to adjust surgical and radiation treatment based on pathologic response and thereby minimize the morbidity of combined therapy. Various clinical scenarios will be presented with treatment options. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr CS01-2.

Pattern of local-regional relapse and survival after bimodality therapy for esophageal cancer: Implications for the surveillance strategy.

4083 Background: Evidence for definitive chemoradiotherapy (bimodality therapy [BMT]) has been established for patients with esophageal and gastroesophageal junction cancer (EGEJC) who do not qualify for surgery. Surveillance for these patients is often recommended but the literature lacks guidance for an evidence-based surveillance strategy after BMT. Methods: We analyzed 276 patients with EGEJC who underwent BMT and had pre- and postchemoradiation endoscopic biopsies and imaging studies available for review. Patients who underwent planned surgery or salvage surgery (SS) within 6 months from BMT were excluded. We reviewed the pattern of relapse over time. Local-regional disease (LRD) after BMT was classified as regional disease (RD) or luminal-only disease (LD). Overall survival (OS) probabilities were estimated using the Kaplan-Meier method and compared using the log-rank test. Results: For 276 patients, the median follow-up time was 53.0 months (95% confidence interval [CI], 47.3-58.7). A total of 184 (66.7%) patients had a persistent disease or relapse after BMT: 120 distant metastases (43.5% of 276) and 64 LRD (23.2% of 276). Of 64 LRD, 58 (91%) were diagnosed within 2 years of BMT and 63 (98%) were diagnosed within 3 years (see Table). Twenty-three of 64 LRD patients underwent SS. For patients with SS, the median OS time from diagnosis of LRD was 58.0 months (95% CI, not reached), and that for patients without SS was 9.0 months (95% CI, 7.3-10.7); this difference was highly significant (p < 0.001). Conclusions: Our data suggest that 91% of LRD occurred within 2 years after BMT and the OS with SS for LRD was better than that without SS. These data can contribute to the development of an evidence-based surveillance strategy. [Table: see text]

Frequency of relapse over time based on baseline stage in esophageal cancer patients treated with definitive chemoradiation (DCRT).

e15013 Background: Evidence for definitive chemoradiotherapy (bimodality therapy [BMT]) has been established for patients with Esophageal and Gastroesophageal Junction cancers (EGEJC) who do not qualify for surgery. Frequency of relapse over time based on baseline clinical stage is not well described. Methods: We analyzed 276 patients with EGEJC who underwent BMT. All the patients had pre- and post- chemoradiation, endoscopic biopsy and imaging study. The type and timing of first relapse or persistent disease after BMT was analyzed using 12-month intervals and was grouped by the baseline stage. Multiple statistical methods were used. Results: For 276 patients, the median follow-up time was 53.0 months (95% confidence interval [CI], 47.3-58.7) and the median overall survival was 27.0months (95% CI, 20.7-33.3). A total of 184 (66.7%) patients had a persistent disease or relapse after BMT: 120 distant metastases (43.5% of 276) and 64 local-regional disease (23.2% of 276). The table below demonstrates that baseline clinical stage has a great deal of influence on the frequency and timing of relapse (see Table). Conclusions: These data demonstrate that relapse timing and patterns are associated with the baseline clinical stage. Our data can contribute to an evidence-based surveillance strategy.[Table: see text]

Patients' experiences following local–regional recurrence of thyroid cancer: A qualitative study

The psychosocial impact of local-regional thyroid cancer recurrence is not known. The aim of this study was to explore thyroid cancer patients' experiences relating to diagnosis and treatment of local-regional disease recurrence. We conducted 15 semi-structured interviews with survivors of differentiated thyroid cancer who underwent neck reoperation for recurrent disease. Participants were recruited from the clinical practices of thyroid surgeons and endocrinologists at University Health Network and Mount Sinai Hospitals in Toronto, Ontario. Participant interviews were audio-recorded, transcribed verbatim, and analyzed using qualitative methods. Saturation of themes was achieved. Local-regional recurrence of thyroid cancer was associated with significant psychological distress. Confidence in healthcare providers as well as psychosocial support from family or social relations, were helpful in coping with disease recurrence. After recovery from treatment, post-traumatic growth was reported. However, questions and worry about the risk for future recurrence lingered at follow-up. Local-regional recurrence of thyroid cancer has a significant psychosocial impact on patients, and support needs are heightened throughout the experience. Healthcare providers should strive to ensure that medical information and psychosocial needs of such patients are met, throughout the treatment experience, as well as at follow-up.

Octreotide LAR use among elderly patients with carcinoid syndrome and survival outcomes: A population-based analysis.

322 Background: Octreotide LAR is indicated for the treatment of carcinoid syndrome, diarrhea related to VIPoma, and may delay tumor growth in neuroendocrine tumors (NETs). The pattern of octreotide LAR use in clinical practice and its impact on survival outcomes has not been well-documented. Methods: Using the SEER-Medicare database, we identified NET patients diagnosed between 7/1999 and 12/2007. We excluded those under age 65, enrolled in HMOs, and without continuous Part A and B enrollment within 12 months of diagnosis. Potential indication for octreotide use was defined as ≥ 2 claims for carcinoid syndrome, flushing, diarrhea, or malignant islet cell neoplasm within first year of diagnosis, with the first claim occurring within 6 months of diagnosis. HCPCS codes, J2352 and J2353, were used to identify octreotide LAR treatment. Multivariate logistic regression and Cox proportional hazard survival analyses were performed to ascertain factors associated with octreotide use and evaluate impact of octreotide use on survival; covariates included age, race, region, comorbidity score, urban/rural status, tumor characteristics, neighborhood socioeconomic status and year of diagnosis. Results: Among those with potential indication for octreotide use (carcinoid syndrome and islet cell), 264 (49%) out of 539 distant stage patients, and 83 (10%) out of 850 patients with local regional disease were started on octreotide LAR within 6 months of diagnosis. Multivariate logistic regression showed that patients living in the southern region were less likely to use octreotide. Multivariate proportional hazard model showed that octreotide LAR provided a significant 5-year survival benefit for distant stage patients (HR=.80, p-value=.047); while this survival benefit was not shown for the local/regional stage patients (HR=.97, p-value=.89). Conclusions: This retrospective study suggests a possible survival benefit for use of octreotide LAR in distant stage elderly patients with carcinoid syndrome. Data also suggest that many elderly patients with claims for carcinoid syndrome did not receive octreotide LAR therapy within 6 months of diagnosis. Further studies and improved education are warranted.

Transoral robotic surgery and adjuvant therapy for oropharyngeal carcinomas and the influence of p16INK4aon treatment outcomes

To determine the prognostic influence of p16(INK4a) immunohistochemistry on the survival of resectable oropharyngeal carcinomas (OPSCC). Retrospective pathologic evaluation of a prospective single-arm cohort study at a tertiary referral center. There were 48 patients with resectable OPSCC who consented for transoral robotic surgery (TORS) and banked tissue specimen for assessment. TORS was with or without adjuvant radiation or chemoradiation. Main outcome measures were p16(INK4a) status, human papillomavirus status, local-regional disease control, and overall, disease-specific, and disease-free survival. p16(INK4a) and HPV positivity were identified in 73% and 74% of patients respectively. With a median follow-up of 38.8 months (2.5-63.3 months), only one local-regional relapse has occurred in both the p16(INK4a)-positive and p16(INK4a) -negative cohorts. No disease-specific, disease-free, and overall survival differences were observed between p16(INK4a) -positive and p16(INK4a)-negative patients (P = .446, P = .277, P = .643, respectively). p16(INK4a) was not prognostic in resectable OPSCC when treated with an initial TORS approach.

Progress in Evaluation of Pathologic Response to Neoadjuvant Chemotherapy of Breast Cancer

Neoadjuvant chemotherapy is provided to patients with locally advanced breast cancer. Its main objective is to bring about a complete pathologic response which is correlated with long term patient survival, a clinical end point of preoperative chemotherapy. Besides, it may downsize the tumor, enabling breast conserving or limited mastectomy. Preoperative chemotherapy also provides the opportunity of assessing the chemosensitivity of the tumor in vivo so that postoperative chemotherapy is tailored according to the outcome of the neoadjuvant chemotherapy. Pathological complete response is considered when there is complete eradication of the local regional disease. Residual disease in the primary focus and/or axilla after preoperative chemotherapy is associated with poor prognosis. Standard preoperative and postoperative specimen collection, handling, processing, and examination are essential components of proper evaluation and reporting of pathologic response to neoadjuvant chemotherapy.

A Neoadjuvant Strategy for the Management of Nonmetastatic Pancreatic Cancer

Treatment of pancreatic cancer has become increasingly multimodal, with patients undergoing chemotherapy, radiation, and surgical extirpation in hope of long-term cures. There is ongoing debate over the timing, sequence, and necessity of these treatments as they pertain to the spectrum of local regional disease. This review examines the literature of a neoadjuvant treatment strategy as stratified by initial tumor evaluation (potentially resectable, borderline resectable, and locally advanced disease), highlighting preoperative emergence of latent metastatic disease, attempted resection rates, margin negative (R0) resection rates, and pathologic response to treatment. Guidelines currently support a neoadjuvant strategy in patients with borderline resectable disease. Although there is currently no high-level evidence to recommend neoadjuvant therapy for all patients, there is suggestive evidence that such a strategy may be beneficial and random-assignment prospective trials are ongoing.

Presentation of contralateral axillary involvement from breast cancer.

49 Background: Metastatic breast cancer to the contralateral axilla is defined as stage IV disease. We postulate that metastatic disease to the contralateral axilla is secondary to extension of aggressive, local regional disease rather than distant metastatic disease and may have a better outcome. Methods: An IRB-approved retrospective review of breast cancer cases presenting to a single institution between January 2005 and December 2011 was performed to identify cases with contralateral axillary disease. Eligibility for the study included unilateral primary breast cancer at presentation with synchronous/metachronous documented metastasis to the contralateral axilla without a documented primary invasive breast cancer within the contralateral breast by surgery or MRI. Clinicopathologic data was recorded for these patients (pts). Results: Thirteen pts were identified that fulfilled eligibility criteria. The average age was 53 years (range 26.3-72.2) with 12/13 (92%) pts presenting with a locally advanced breast tumor or an ipsilateral in-breast recurrence. 10/13 (77%) pts had documented dermal involvement of tumor either at presentation or local recurrence. Contralateral metastatic disease occurred synchronously with the initial primary tumor (3pts, 23%), concomitant with a local recurrence (5 pts, 38%), metachronously with the initial tumor in (3pts, 23%), and metachronously with a local recurrence in (2pts, 15%). Resection of involved contralateral nodes was performed in 10/13 (77%) pts; 5/13 (38%) patients received contralateral axillary radiation; all 13 (100%) received systemic therapy. 9/13 pts (69%) developed distant metastatic disease with a mean follow up of 2.6 years (range 0.3-6.8 years). 3/13 pts (23%) have no evidence of disease at a mean follow up of 4.7 years (range 1.5-6.8). Conclusions: Contralateral axillary spread of breast cancer carries a poor prognosis but may have different prognostic implications than metastatic disease. Contralateral axillary metastatic disease may occur through dermal lymphatic spread and requires multidisciplinary management. Further study is warranted on the prognosis and management of these challenging and rare cases.

Nasopharyngeal carcinoma treated by intensity-modulated radiotherapy: long-term results of 416 patients

Objective To summarize the long term outcomes and prognostic factors of nasopharyngeal carcinoma (NPC) treated by intensity-modulated radiotherapy.Methods From Nov 2001to Dec 2009,totally 416 newly diagnosed NPC patients was treated in our hospital.The prescribed dose was 70-78 Gy to the gross tumor volume and 70 Gy to the positive neck nodes,60 Gy to the clinical target volume,and 50-56 Gy to the clinically negative neck.Among 333 stage Ⅲ/Ⅳ patients according to the 2010 UICC staging system,187 received concurrent chemoradiotherapy with a regimen of weekly cisplatin 30mg/m2.Local control rate (LC),overall survival (OS),disease-hree survival (DFS) and distant metastasis-free survival (DMFS) were estimated using the Kaplan-Meier method.Results The follow up rate is 98.0％.158 patients was followed up more than 5 years.The 5 years LC,OS,DFS and DMFS of whole group were 87.7％,82.1％,71.8％ and 84.5％.Sex,Age,T stage and N stage were independent prognostic factors for OS (x2=4.59,11.20,19.40,18.00,P=0.03,0.00,0.00,0.00),T and N stage were independent prognostic factors for DFS (x2=33.50,21.20,P=0.00,0.00) and DMFS (x2=11.90,14.60,P=0.01,0.01).The 5 years LC,OS,DFS and DMFS for local-regional advanced disease with or without concurrent chemotherapy was 82.2％ and 90.7％ (x2=1.72,P=0.19),70.2％ and 83.4％ (x2=1.42,P=0.23),62.8％ and 73.2％ (x2=2.83,P=0.09),78.0％ and 83.2％ (x2=0.37,P=0.55)respectively.Conclusions The long term outcomes of nasopharyngeal carcinoma treated by intensitymodulated radiotherapy was encouraged.The role of concurrent chemoradiotherapy for locally advanced nasopharyngeal carcinoma treated by intensity-modulated radiotherapy needs further investigated. Key words: Nasopharyngeal neoiplasms/intensity-modulated radiotherapy; Nasopharyngeal neoiplasms/concurrent chemoradiotherapy; Prognosis

Anaplastic Thyroid Carcinoma

Thyroid cancers represent about 1% of all human cancers. Differentiate thyroid carcinomas (DTCs), papillary and follicular cancers, are the most frequent forms, instead Anaplastic Thyroid Carcinoma (ATC) is estimated to comprise 1–2% of thyroid malignancies and it accounts for 14–39% of thyroid cancer deaths. The annual incidence of ATC is about one to two cases/million, with the overall incidence being higher in Europe (and area of endemic goiter) than in USA. ATC has a more complex genotype than DTCs, with chromosomal aberrations present in 85–100% of cases. A small number of gene mutations have been identified, and there appears to be a progression in mutations acquired during dedifferentiation. The mean survival time is around 6 months from diagnosis an outcome that is frequently not altered by treatment. ATC presents with a rapidly growing fixed and hard neck mass, often metastatic local lymph nodes appreciable on examination and/or vocal paralysis. Symptoms may reflect rapid growth of tumor with local invasion and/or compression. The majority of patients with ATC die from aggressive local regional disease, primarily from upper airway respiratory failure. For this reason, aggressive local therapy is indicated in all patients who can tolerate it. Although rarely possible, complete surgical resection gives the best chance of long-term control and improved survival. Therapy options include surgery, external beam radiation therapy, tracheostomy, chemotherapy, and investigational clinical trials. Multimodal or combination therapy should be useful. In fact, surgical debulking of local tumor, combined with external beam radiation therapy and chemotherapy as neoadjuvant (before surgery) or adjuvant (after surgery) therapy, may prevent death from local airway obstruction and as best may slight prolong survival. Investigational clinical trials in phase I or in phase II are actually in running and they include anti-angiogenetic drugs, multi-kinase inhibitor drugs.

Influence of Noncompliance With Radiation Therapy Protocol Guidelines and Operative Bed Recurrences for Children With Rhabdomyosarcoma and Microscopic Residual Disease: A Report From the Children's Oncology Group

Postoperative radiation therapy (RT) is recommended for patients with rhabdomyosarcoma having microscopic disease. Sometimes RT dose/volume is reduced or omitted in an attempt to avoid late effects, particularly in young children. We reviewed operative bed recurrences to determine if noncompliance with RT protocol guidelines influenced local-regional control. All operative bed recurrences among 695 Group II rhabdomyosarcoma patients in Intergroup Rhabdomyosarcoma Study Group (IRS) I through IV were reviewed for deviation from RT protocol. Major/minor dose deviation was defined as >10% or 6-10% of the prescribed dose (40-60 Gy), respectively. Major/minor volume deviation was defined as tumor excluded from the RT field or treatment volume not covered by the specified margin (preoperative tumor volume and 2- to 5-cm margin), respectively. No RT was a major deviation. Forty-six of 83 (55%) patients with operative bed recurrences did not receive the intended RT (39 major and 7 minor deviations). RT omission was the most frequent RT protocol deviation (19/46, 41%), followed by dose (17/46, 37%), volume (9/46, 20%), and dose and volume deviation (1/46, 2%). Only 7 operative bed recurrences occurred in IRS IV (5% local-regional failure) with only 3 RT protocol deviations. Sixty-three (76%) patients with recurrence died of disease despite retrieval therapy, including 13 of 19 nonirradiated children. Over half of the operative bed recurrences were associated with noncompliance; omission of RT was the most common protocol deviation. Three fourths of children die when local-regional disease is not controlled, emphasizing the importance of RT in Group II rhabdomyosarcoma.

ACR Appropriateness Criteria ®: Local–Regional Therapy for Resectable Oropharyngeal Squamous Cell Carcinomas

The optimal management of resectable oropharyngeal squamous cell carcinomas is controversial with many treatment options, both surgical and nonsurgical approaches, supported by published experiences with no randomized trials comparing commonly accepted treatments. The treatment decisions are further complicated by the need for local-regional disease control and competing goals to preserve salivary and swallow function. Treatment decisions may also be affected by tumor and patient related factors and a history of environmental exposure to tobacco and evidence of human papilloma virus. We summarize the published literature and provide treatment consensus derived from the modified Delphi methodology.

Analysis of Super-low Anterior Resection for Rectal Cancer from a Single Center

The purpose of this study was to evaluate the outcome and genitourinary complications of super-low anterior resection (SLAR) followed by adjuvant radiochemotherapy in the management of patients with low rectal cancer. One hundred and six low rectal cancer patients managed with SLAR were analyzed retrospectively. There were seven patients who failed to follow up, and the 5-year survival rate was 65.7% (65/99). There were 35 patients (35.4%) who developed distant metastases, and 12 (12.1%) had local recurrence. The local recurrence rates were 21.1% (4/19), 7.1% (2/28), 5.9% (1/17), and 0% (0/2) in the patients with tumor distance of less than or equal to 2 cm, ranging from 2.1 to 3.0, from 3.1 to 4.0, from 4.1 to 5.0, and more than 5 cm, respectively. This implied local recurrence rate increased against the distance between the lower margin of tumor and resection line. Ninety-eight of 106 rectal patients had complete data of questionnaire: 58 scored 1, 32 scored 2, 7 scored 3, and 1 score 4. This revealed that the fecal function of most patients (91.8%, 90/98) was normal or nearly normal. Twenty-four of 37 males suffered from sexual dysfunction, and among them, eight were impotent (all older than 70years), and 29 had retrograde ejaculation. Meanwhile, seven of 35 females suffered from sexual problem, 1 had dyspareunia, seven had decreased lubrication, and one had inability to achieve orgasm. SLAR followed by adjuvant radiochemotherapy can effectively control local-regional disease and can be one choice of avoiding the functional morbidity of abdominoperineal resection.

Survival outcomes with the use of surgery in limited‐stage small cell lung cancer

Although chemotherapy and radiation therapy currently are recommended in limited-stage small cell lung cancer (L-SCLC), several small series have reported favorable survival outcomes in patients who underwent surgical resection. The authors of this report used a US population-based database to determine survival outcomes of patients who underwent surgery. The Surveillance, Epidemiology, and End Results (SEER) registry was used to identify patients who were diagnosed with L-SCLC between 1988 and 2002 coded by SEER as localized disease (T1-T2Nx-N0) or regional disease (T3-T4Nx-N0). Kaplan-Meier and Cox regression analyses were used to compare overall survival (OS) for all patients. In total, 14,179 patients were identified, including 863 patients who underwent surgical resection. Surgery was associated more commonly with T1/T2 disease (P < .001). Surgery was associated with improved survival for both localized disease and regional disease with improvements in median survival from 15 months to 42 months (P < .001) and from 12 months to 22 months (P < .001), respectively. Lobectomy was associated with the best outcome (P < .001). Patients with localized disease who underwent lobectomy with had a median survival of 65 months and a 5-year OS rate of 52.6%; whereas patients who had regional disease had a median survival of 25 months and a 5-year OS rate of 31.8%. On multivariate analysis, the benefit of surgery varied in a time-dependant fashion. However, the benefit of lobectomy remained across all time intervals (P = .002). The use of surgery, and particularly lobectomy, in selected patients with L-SCLC was associated with improved survival outcomes. Future prospective studies should consider the role of surgery as part of the multimodality management of this disease.

How Will the '4:1 Ratio' Change with Increasingly Effective Systemic Therapy.

Abstract The 4:1 ratio between a reduction in local recurrence at 5 years and a reduction in mortality at 15 years has been well established in clinical practice. The Ratio is particularly useful to estimate the survival benefit of adding RT, particularly in the postmastectomy setting where the use of RT is not routine. It is worth noting, however, that the 4:1 ratio is an average effect that is largely based on trials without systemic therapy and does not account for the interrelated issues of (1) competing risks of local recurrence and distant metastases, (2) biologic heterogeneity, and (3) the impact of (improving) systemic therapy. If the ratio becomes less than 4:1, it means that local treatment is even more important for long-term survival. In this talk, emerging data will be presented illustrating how the '4:1 ratio' is influenced by competing risks of local recurrence and distant metastases, biologic heterogeneity, and the impact of improving systemic therapy. The current data suggest that over the short to intermediate time frame, with increasingly effective systemic therapy, the risk of LR will be less, but the ratio will also be less. Current systemic therapy is most effective in the setting of microscopic residual disease or micrometastases. As systemic therapies are better able to sterilize distant disease, improvements in local-regional control have become more important. As systemic therapy continues to improve such that it can control both distant and local-regional disease, the eventual goal is that local therapy could be completely eliminated; however, that is likely to be sometime into the future. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr MS3-2.

Long-Term Outcomes of Patients with Newly Diagnosed NK/T-Cell Lymphoma Treated by EPOCH Regimen.

Abstract 2689Poster Board II-665 Introduction:Extranodal NK/T-cell lymphoma (ENKL) is a distinct clinicopathological entity of non-Hodgkin's lymphoma, which is characterized by a highly aggressive clinical process and poor prognosis. There are no standard treatment strategies available now. The present study aimed to evaluate the treatment outcome and toxicity of EPOCH regimen for ENKL. Methods:From June 2003 to June 2008, 34 patients including 30 nasal ENKL (88.2%) and 4 extranasal ENKL (11.8%) received doxorubicin, vincristine, etoposide over 96 hours infusion with bolus cyclophosphamide and oral predinisone (EPOCH) combination as first-line treatment. By the Ann Arbor lymphoma Staging Classification, 29 patients (85.3%) had stage ±E-IIE disease and 5 patients (14.7%) had stage IIIE-‡WE disease. Median cycles of EPOCH regimen administered were 2.5 (range from 1 to 6 cycles). Additional involved field radiation therapy (IFRT) was administered to patients with localized regional disease after chemotherapy. Results:Among 34 patients, 33 were eligible for objective response evaluation. The response rate (RR) for the whole group was 60.6% (20/33) with complete remission (CR) rate of 45.5% (15/33). The RR of patients with nasal ENKL was 66.7% (20/30), the CR rate was 50% (15/30). Of the 4 patients with extranasal ENKL, only one achieved stable disease (SD), the other three had progressive disease (PD) during chemotherapy. After a median follow-up of 22 (2–68) months, the estimated overall 3-year overall survival rate (OS) was 52.2%. For patients with nasal ENKL, the estimated median survival time was not reached, the 3-year OS was 59.4%. For patients with extranasal ENKL, the estimated median survival time was only 7 months. For stage ±E-IIE patients with nasal ENKL who received initial EPOCH chemotherapy followed IFRT, the CR rate was 75.0%, and the 3-year survival rate was 75.0%. 102 cycles of chemotherapy were administered to 34 patients. Major adverse effect was myelosuppression. The incidence of grade III-‡W neutropenia was 30.9% and 60 cycles needed G-CSF support. Other toxicities were mild, no treatment-related mortality occurred. Conclusion:EPOCH regiment was effective on ENKL with acceptable toxlicity. EPOCH followed by IFRT yielded promising outcome for patients with localized nasal ENKL. However, patients with extranasal ENKL responded poorly, and more efficacious treatment strategies are urgently needed. Disclosures:No relevant conflicts of interest to declare.

Chordoma of the Mobile Spine and Sacrum: A Retrospective Analysis of a Series of Patients Surgically Treated at Two Referral Centers

Chordoma is a rare tumor, and its natural history is still not well known. All patients affected by localized chordoma surgically treated at Istituto Ortopedico Rizzoli, Bologna, and Istituto Nazionale Tumori, Milan, Italy, between 1980 and 2008 were reviewed. Local recurrence, distant metastasis, and overall survival (OS) were analyzed both from time of diagnosis and from time of local recurrence/distant metastasis. A multivariable analysis to identify independent prognostic factors was carried out. A total of 138 consecutive patients were identified (sacrum 78%, lumbar spine 15%, cervical-dorsal spine 7%). Of these, 130 underwent surgical resection. Median follow-up was 142 months. The 5- and 10-year OS, local relapse-free survival (LRFS), and distant relapse-free survival (DRFS) were, respectively, 78% and 54%, 52% and 33%, and 86% and 72%. Size was an independent prognostic factor for OS (P value < .001), LRFS (P value: .038), and DRFS (P value: .004), while surgical margins independently predicted LRFS (P value: .003) with a trend for OS. The 5- and 10-year OS, LRFS, and DRFS after the first local relapse were 50% and 26%, 47% and 31%, and 64% and 61%. The size of the recurrence and quality of surgical margins did not influence postrelapse OS. The 5-year OS after the second local relapse was 19%. 22% of patients developed distant metastases with a 5-year post-metastases OS of 33%. Tumor size and surgical margins affected outcome only on initial presentation. However, wide surgery was feasible in a minority of cases. Most patients died of local-regional disease even when metastases occurred. Indeed, long-term prognosis was such that disease-free survival at 10 years was only 26%.