Freedom From Local Recurrence Research Articles

Long-Term Clinical Outcomes, Late Toxicities, and Cosmetic Results of Short-Course Two-Day Brachytherapy Accelerated Partial Breast Irradiation

Hypofractionated radiotherapy is increasingly being adopted for early-stage breast cancer. To assess the long-term outcome of 2-day brachytherapy accelerated partial breast irradiation [2d-APBI], we analyzed patients so treated for clinical effectiveness, late toxicity, and cosmetic results. Between 3/2004 and 8/2007, 45 patients were treated with single-lumen applicator-based 2d-APBI [700 cGy BID x 4]. Updated thru 1/2017, an IRB-approved retrospective review was done. Selection criteria included age >40, ≤3.0 cm tumor size, ≤3 pathologically positive lymph nodes, and negative margins (per NSABP guidelines). Based upon the ASTRO Consensus Statement guidelines for APBI (2009) applied retrospectively, 15 were suitable (33%), 27 cautionary (60%), and 3 unsuitable (7%). Freedom from local recurrence (FFLR), regional recurrence (FFRR), distant metastasis (FFDM), contralateral breast cancer (CLBC), disease-free survival (DFS), cause-specific survival (CSS), and overall survival (OS) were assessed by Kaplan-Meier. Toxicities were scored using CTCAE v3.0. Cosmetic rating was scored via the Harvard criteria. Median follow-up was 9.4 years. Fourteen patients were followed ≥ 10 yrs (31%) and 17 with follow-up of 9.0 - 9.9 yrs (38%). Median age was 66 yrs (48-83 yrs) with most having T1 tumors (96%) [median size 0.6cm]; all had margins with no tumor on ink. A minority (4%) had positive regional nodes. ER positivity was found in 73%. Endocrine therapy was received by 61%, while 18% had chemotherapy. Clinical outcomes revealed FFLR 97.4%, FFRR 100%, FFDM 92.9%, CLBC 97.4%, DFS 90.3%, CSS 97.6%, and OS 79.0%, all 10-year actuarial. Late toxicities analyzed included skin pigmentation, edema, and pain (all grade 1/2) along with telangiectasias, induration (Table 1), fat necrosis, seroma and rib fracture. No grade 3 or 4 toxicities were noted except for 2% grade 3 telangiectasias and 2% grade 3 induration. Fat necrosis was seen in 14% and persistent seroma in 17%. Rib fracture was seen in 3 (7%) where 160% of the prescription dose was accepted during this treatment era. Cosmesis was good/excellent in 88% at 10 years. With median follow-up approaching 10 years, 2-day APBI demonstrates excellent clinical effectiveness, minimal late morbidity, and good/excellent cosmesis in the majority of patients. Dose constraints such as to ribs/chest wall have been refined from these results. Short-course APBI affords appropriately selected early-stage breast cancer patients irradiation in 2 days vs several weeks of whole breast external beam treatments. Further follow-up of 2-day APBI patients will be needed to substantiate these long-term findings.Abstract 1100; Table 1Chronic toxicities with 2-day APBI (n = 42)Toxicity GradeGrade 0Grade 1Grade 2Grade 3Hyperpigmentation24 (57%)17 (41%)1 (2%)Hypopigmentation37 (88%)5 (12%)Breast Pain26 (60%)14 (33%)2 (5%)Breast Edema28 (67%)12 (28%)2 (5%)Induration/Fibrosis7 (17%)14 (33%)20 (48%)1 (2%)Telangiectasia28 (67%)6 (14%)7 (17%)1 (2%) Open table in a new tab

Local radiotherapy alone following neoadjuvant chemotherapy and surgery in combined clinical stage II and III breast cancer.

PurposeThe outcomes and recurrence patterns for patients with combined clinical stage II and III breast cancer treated with local but not regional radiotherapy after neoadjuvant chemotherapy (NAC) and surgery are poorly documented.MethodsWe performed a retrospective review of a prospectively collected database comprised of breast cancer patients who received NAC at our institution. 172 patients met the specified criteria of receiving NAC, surgery inclusive of axillary nodal dissection and post-operative local (but not regional) radiotherapy.ResultsOne hundred eleven patients (64.5 %) were of combined clinical stage II and 61 (35.5 %) stage III at diagnosis. 103 patients (59.9 %) were clinically node positive with 101 cN1. On post-NAC pathology 29 (16.9 %) patients had a complete response, 30 (17.6 %) were combined yp stage I, 104 (60.5 %) yp stage II and 9 (5.2 %) yp stage III. 77 (44.8 %) were node positive on post-NAC pathology, all ypN1. 52.3 % were treated with breast conservation. At a median follow up of 67 months, 56 patients experienced breast cancer recurrence and 47 had died with breast cancer the dominant cause. Actuarial 5 and 10 year estimated freedom from locoregional recurrence (FFLRR), freedom from distant metastases (FFDM), disease free (DFS) and overall survival (OS) were 90 and 83.5, 74.5 and 64, 69.5 and 56, 79.5 and 65 % respectively. The most common pattern of failure was distant alone (without local or regional failure). Regional failure as the only site of first failure occurred in just three patients but was a component of first failure in a further twelve. Predictive factors on multivariate analysis for FFLRR were clinical stage II and estrogen receptor positivity. Prognostic factors were ypN0 stage and estrogen receptor positive status.ConclusionsLocal radiotherapy alone may be reasonable for selected patients. Isolated distant recurrence is the dominant mode of failure for breast cancer patients who have received local radiotherapy without regional coverage following NAC.

Resected pN1 non-small cell lung cancer: recurrence patterns and nodal risk factors may suggest selection criteria for post-operative radiotherapy.

To describe the pattern of recurrence in resected pN1 non-small cell lung cancer (NSCLC) and to identify factors predicting an increased risk of locoregional recurrence (LR) or distant metastasis (DM) to define a selected population who may benefit from postoperative radiotherapy (PORT). 285 patients with resected pN1 NSCLC were identified. Patients with positive surgical margins, undergoing neoadjuvant treatment or PORT, were excluded. LR was defined as first event of recurrence at the surgical bed, ipsilateral hilum or mediastinum, and other sites were considered as DM. Kaplan-Meier actuarial estimates of overall survival (OS), progression-free survival (PFS), freedom from LR (FFLR) and freedom from DM (FFDM) in different subgroups were compared with the log-rank test. Multivariate analysis was calculated. 202 patients met the inclusion criteria, 24% received adjuvant chemotherapy. The median follow-up was 39months. The total number of recurrences was 118 (64.4%): 44 (24%) and 74 (40.4%) for LR and DM, respectively. Five-year OS and PFS rates were 39.2 and 33.3%, respectively. Extra capsular extension (ECE) (RR 2.10, p=0.01) and lymph nodal ratio (LNR) >0:15 (RR 1.68, p=0.015) were associated with a worse PFS. ECE and LNR >0.15 were significantly related to a worst FFLR (RR 3.04 and 4.42, respectively), and adenocarcinoma to an unfavorable FFDM (RR 1.97, p=0.013). Nodal factors as high LNR and ECE can predict an increased risk of worse FFLR and PFS. Prospective data on selected patients, treated with modern radiotherapy techniques, need to be collected to re-evaluate the role of radiotherapy.

Abstract P3-12-21: Post-mastectomy radiotherapy for T3N0 breast cancers: A retrospective, multi-institution review

Abstract Purpose The role of post-mastectomy radiotherapy (PMRT) for node-negative breast cancers that are larger than five centimeters remains undefined. The purpose of this study was to report outcomes for women with T3N0 breast cancers treated with and without PMRT. Methods T3N0 breast cancers diagnosed between 1985 and 2014 were collected from the tumor registries of two large healthcare systems. For the purpose of our analysis, patients were divided into two groups: (1) women who received PMRT and (2) those who did not receive PMRT. Chi-square and students t-tests were used to compare baseline characteristics. Kaplan Meier estimates were used to analyze freedom from locoregional recurrence (FFLR), relapse free survival (RFS), and overall survival (OS). Results This analysis identified 93 women with T3N0 breast cancers. Of these, 53 received PMRT and 40 did not. Median follow up was 6.2 years and 5.3 years in the non-PMRT and PMRT cohorts, respectively. Women not undergoing PMRT were more likely to be diagnosed in the 1980s and 1990s than women receiving PMRT (p< 0.05). Adjuvant chemotherapy and endocrine therapy were less frequently given in patients not receiving PMRT (p<0.05), again associated with an earlier treatment era. There was a trend toward increased FFLR in the women receiving PMRT (p=0.15). FFLR in the PMRT cohort was 97.9% and 97.9% at five and ten years, respectively. For women not receiving PMRT, FFLR was 88.4% and 88.4% at five and ten years, respectively. RFS (p=0.66) and OS (p=0.48) were similar. Conclusions Women not receiving PMRT in our study had a locoregional failure rate of only 11.6% at ten years despite receiving inferior systemic treatment by current standards. Locoregional control after PMRT for T3N0 breast cancers was excellent with a 2.1% failure rate at ten years. Further research is needed to define PMRT indications for this patient population when receiving chemotherapy and endocrine therapy in line with current guidelines. Citation Format: Frandsen JE, Cannon G, Poppe M. Post-mastectomy radiotherapy for T3N0 breast cancers: A retrospective, multi-institution review. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-12-21.

Adjuvant pelvic radiotherapy in patients with stage IVA rectal adenocarcinoma.

711 Background: For patients with stage IVA rectal cancer with liver metastases treated with curative-intent chemotherapy and surgery, the role of adjuvant pelvic radiotherapy (RT) is unclear. The purpose of this study was to evaluate the impact of pelvic RT on oncologic outcomes in this patient population. Methods: We retrospectively reviewed medical records of all patients with stage IVA rectal adenocarcinoma with liver metastases treated with curative-intent resection of the primary tumor and all liver metastases at our institution between 1991 and 2010. Patient and treatment characteristics were compared between patients who did or did not receive pelvic RT using chi-square and unpaired ttests. Survival and recurrence estimates were calculated from date of initial diagnosis using the Kaplan-Meier method. Local recurrence (LR) was defined as recurrence in the pelvis occurring at or before distant recurrence (DR). Cox regression was used to compare rates of freedom from LR (FFLR), freedom from DR (FFDR), and overall survival (OS) between patients who did or did not receive pelvic RT. Results: The analysis included 65 patients. Median patient age at diagnosis was 59 years (range, 27-87). Tumor stage was T2 (n = 4), T3 (n = 53), or T4 (n = 8). The median number of liver metastases was 2 (range, 1-14). Surgery was low anterior resection (n = 54) or abdominoperineal resection (n = 11). All patients received perioperative fluoropyrimidine based chemotherapy. Pelvic RT was administered to 35 patients (54%), either preoperatively (n = 22) or postoperatively (n = 13). Median RT dose was 50.4 Gy (range 25-58). Patient characteristics were similar for those who did or did not receive pelvic RT. Median follow-up was 3.7 years. The 3-year estimates of FFLR, FFDR and OS were 81% vs 58% (p =.056), 35% vs 29% (p =.75), and 66% vs 71% (p =.81) for RT vs no RT, respectively. Conclusions: In this analysis of patients with stage IVA rectal cancer with liver metastases undergoing curative intent therapy, pelvic RT (vs. no pelvic RT) was associated with a trend to lower rates of LR and similar rates of DR and OS.

Promising results with image guided intensity modulated radiotherapy for muscle invasive bladder cancer

AimTo describe the feasibility of image guided intensity modulated radiotherapy (IG-IMRT) using daily soft tissue matching in the treatment of bladder cancer.MethodsTwenty-eight patients with muscle-invasive carcinoma of the bladder were recruited to a protocol of definitive radiation using IMRT with accelerated hypofractionation with simultaneous integrated boost (SIB). Isotropic margins of .5 and 1 cm were used to generate the high risk and intermediate risk planning target volumes respectively. Cone beam CT (CBCT) was acquired daily and a soft tissue match was performed. Cystoscopy was scheduled 6 weeks post treatment.ResultsThe median age was 83 years (range 58-92). Twenty patients had stage II or III disease, and eight were stage IV. Gross disease received 66 Gy in 30 fractions in 11 patients (ten with concurrent chemotherapy) or 55 Gy in 20 fractions for those of poorer performance status or with palliative intent. All patients completed radiation treatment as planned. Three patients ceased chemotherapy early due to toxicity. Six patients (21 %) had acute Grade ≥ 2 genitourinary (GU) toxicity and six (21 %) had acute Grade ≥ 2 gastrointestinal (GI) toxicity. Five patients (18 %) developed Grade ≥2 late GU toxicity and no ≥2 late GI toxicity was observed.Nineteen patients underwent cystoscopy following radiation, with complete response (CR) in 16 cases (86 %), including all patients treated with chemoradiotherapy. Eight patients relapsed, four of which were local relapses. Of the patients with local recurrence, one underwent salvage cystectomy. For patients treated with definitive intent, freedom from locoregional recurrence (FFLR) and overall survival (OS) was 90 %/100 % for chemoradiotherapy versus 86 %/69 % for radiotherapy alone.ConclusionIG- IMRT using daily soft tissue matching is a feasible in the treatment of bladder cancer, enabling the delivery of accelerated synchronous integrated boost with good early local control outcomes and low toxicity.

FDG-PET maximum standardized uptake value is prognostic for recurrence and survival after stereotactic body radiotherapy for non-small cell lung cancer.

Glucose metabolic activity measured by [(18)F]-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) has shown prognostic value in multiple malignancies, but results are often confounded by the inclusion of patients with various disease stages and undergoing various therapies. This study was designed to evaluate the prognostic value of tumor FDG uptake quantified by maximum standardized uptake value (SUVmax) in a large group of early-stage non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiotherapy (SBRT) using consistent treatment techniques. Two hundred nineteen lesions in 211 patients treated with definitive SBRT for stage I NSCLC were analyzed after a median follow-up of 25.2 months. Cox regression was used to determine associations between SUVmax and overall survival (OS), disease-specific survival (DSS), and freedom from local recurrence (FFLR) or distant metastasis (FFDM). SUVmax >3.0 was associated with worse OS (p<0.001), FFLR (p=0.003) and FFDM (p=0.003). On multivariate analysis, OS was associated with SUVmax (HR 1.89, p=0.03), gross tumor volume (GTV) (HR 1.94, p=0.005) and Karnofsky performance status (KPS) (HR 0.51, p=0.008). DSS was associated only with SUVmax (HR 2.58, p=0.04). Both LR (HR 11.47, p=0.02) and DM (HR 3.75, p=0.006) were also associated with higher SUVmax. In a large patient population, SUVmax >3.0 was associated with worse survival and a greater propensity for local recurrence and distant metastasis after SBRT for NSCLC.

Risk factors for locoregional recurrence in patients with resected N1 non-small cell lung cancer: a retrospective study to identify patterns of failure and implications for adjuvant radiotherapy

BackgroundMeta-analysis of randomized trials has shown that postoperative radiotherapy (PORT) had a detrimental effect on overall survival (OS) in patients with resected N1 non–small cell lung cancer (NSCLC). Conversely, the locoregional recurrence (LR) rate is reported to be high without adjuvant PORT in these patients. We have evaluated the pattern of failure, actuarial risk and risk factors for LR in order to identify the subset of N1 NSCLC patients with the highest risk of LR. These patients could potentially benefit from PORT.MethodsWe conducted a retrospective study on 199 patients with pathologically confirmed T1–3N1M0 NSCLC who underwent surgery. None of the patients had positive surgical margins or received preoperative therapy or PORT. The median follow-up was 53.8 months. Complete mediastinal lymph node (MLN) dissection and examination was defined as ≥3 dissected and examined MLN stations; incomplete MLN dissection or examination (IMD) was defined as <3 dissected or examined MLN stations. The primary end point of this study was freedom from LR (FFLR). Differences between patient groups were compared and risk factors for LR were identified by univariate and multivariate analyses.ResultsLR was identified in 41 (20.6%) patients, distant metastasis (DM) was identified in 79 (39.7%) patients and concurrent LR and DM was identified in 25 (12.6%) patients. The 3- and 5-year OS rates in patients with resected N1 NSCLC were 78.4% and 65.6%, respectively. The corresponding FFLR rates were 80.8% and 77.3%, respectively. Univariate analyses identified that nonsmokers, ≤23 dissected lymph nodes, visceral pleural invasion and lymph node ratio >10% were significantly associated with lower FFLR rates (P < 0.05). Multivariate analyses further confirmed positive lymph nodes at station 10 and IMD as risk factors for LR (P < 0.05). The 5-year LR rate was highest in patients with both these risk factors (48%).ConclusionsThe incidence of LR in patients with surgically resected T1–3N1M0 NSCLC is high. Patients with IMD and positive lymph nodes at station 10 have the highest risk of LR, and may therefore benefit from adjuvant PORT. Further investigations of PORT in this subset of patients are warranted.

Concurrent chemoradiotherapy with or without adjuvant chemotherapy in intermediate and locoregionally advanced nasopharyngeal carcinoma

Concurrent chemoradiotherapy (CCRT) showed a significant improvement in disease control and clinical outcome in patients with intermediate and locoregionally advanced nasopharyngeal carcinoma (NPC) (stage II, III and IVA+B). However, there has been debate about the contribution and application of additional adjuvant chemotherapy (AC) to a CCRT regime. This study aims to evaluate the additional value of AC in the treatment of intermediate and locally advanced NPC with regard to toxicity and clinical outcomes. A total of 189 patients with American Joint Committee on Cancer (AJCC) stage II to stage IVB NPC were retrospectively identified. Patient characteristics, toxicity, compliance with treatment and clinical outcomes, including response to treatment, overall survival (OS), progression-free survival (PFS), relapse-free survival (RFS), freedom from local recurrence (FLR) and freedom from distant metastasis (FDM), were analyzed. The overall response rate of CCRT and CCRT/AC groups was 97.92 % and 97.83 %, respectively (P=0.643). The 5-year OS rate was 68.2 % in the CCRT group and 75.9 % in the CCRT/AC group (P=0.53). The 5-year PFS rate was 66.7 % and 71.4 % in CCRT and CCRT/AC groups, respectively (P=0.96). This study showed no evidence of an additional value of AC in CCRT treatment in disease control and clinical outcomes in patients with locally advanced NPC in endemic regions. Moreover, three additional cycles of AC after CCRT appeared to be poorly tolerated in patients. Therefore, AC should not be routinely used for treatment, although clinical trials may be justified.

Dose-escalated adaptive image-guided radiotherapy versus high-dose-rate brachytherapy monotherapy for low-risk prostate cancer.

145 Background: Both IGRT and HDR are used for definitive treatment of low-risk prostate. No comparative study of these contemporary modalities exists. Methods: Charts for patients with low-risk prostate cancer by NCCN criteria treated 1999-2012 were reviewed. For IGRT, the clinical target volume (CTV) included the prostate and proximal seminal vesicles. A CT-based, off-line adaptive treatment plan was made with a patient-specific confidence-limited planning target volume (cl-PTV) based on the planning plus four additional daily CT scans. Overall survival (OS) was calculated by the Kaplan-Meier method (log-rank test), with Cox regression for uni- and multi-variate analysis. Cumulative incidence (Gray’s test), with competing risks analysis (Fine and Gray) were used for biochemical control (BC) and freedom from local recurrence (FFLR). Results: There were 598 IGRT and 399 HDR patients (see Table), with a median follow-up of 6.1 and 3.6 years, respectively (p&lt;0.001). The median prescribed IGRT dose was 75.6 Gy (range 73.8-79.2). HDR doses were 24 Gy (n=126) or 27 Gy (n=151) in 2 fractions, or 36 Gy (n=3) or 38 Gy (n=335) in 4 fractions. Five- and 10-year BC was 99% and 94% for IGRT and 98% and 95% for HDR (p=0.77); FFLR was 100% and 99% for both (p=0.89); and OS was 95% and 75% for IGRT and 97% and 85% for HDR (p=0.04). On multivariate analysis, predictors (p&lt;0.10) for OS were age (p&lt;0.001) and PNI (p=0.04); for LR, PPC (p=0.01); and for BC, a trend for PSA (p=0.08). Treatment type was not a predictor of OS, BC or FFLR (p&gt;0.5). Conclusions: Both dose- escalated IGRT and HDR monotherapy yield similarly excellent outcomes for low-risk prostate cancer. Our experience supports the continued use of brachytherapy as monotherapy in low-risk prostate cancer. [Table: see text]

The Role of a Boost Radiation Dose in Patients with Negative Re-Excision Findings

The aim of this study is to evaluate whether patients who have no residual tumor at the time of a re-excision lumpectomy benefit from the addition of a radiation boost dose. The records of 535 patients treated with breast- conserving therapy (BCT) for Stage I-II breast cancer were reviewed. The actuarial risk of local recurrence (LR) was determined for the 262 patients in this cohort who underwent re-excision lumpectomy. There was no significant difference in the 10-year freedom from local recurrence (FFLR) for patients with negative re-excisions (96%) compared to patients with residual tumor that was adequately excised (92%). Patients with residual tumor at or close to the final margins, however, had a significantly lower FFLR (80%; p=.01). The FFLR for patients with negative re-excisions was 97% for patients not receiving a boost (n=94) and 95% for patients who received a boost (n=74) (p=ns). For patients <50, FFLR was 96% with a boost and 87% without a boost (p=ns). Extensive intraductal component was the only significant predictor of LR among patients with negative re-excisions (p=.02). The presence of residual disease in the re-excision specimen did not predict for LR as long as the final margins were negative. Among patients with negative re-excisions, the boost did not significantly improve local control. There was a trend for better outcomes, however, in younger patients treated with a boost even in the setting of a negative re-excision. Due to the limitations of the retrospective nature of this study, it will be important to address this question in a prospective fashion before making any definitive conclusions or changes in current clinical practice.

Relapse patterns in WHO 2/3 nasopharyngeal cancer: Is there a difference between ethnic Asian vs. non-Asian patients?

The purpose of this study was to assess whether ethnicity is an independent prognostic factor in patients with World Health Organization (WHO) type 2 or 3 nasopharyngeal carcinoma (NPC). Specifically, we examined the patterns of relapse observed in patients classified as "Asian" (born in southern China or southeast Asia) or "non-Asian" (born in Australia, Europe, the Middle East, or the Pacific Islands). All patients planned for radical treatment at the Peter MacCallum Cancer Centre from April 1985 to December 1999 were included in this study. Pathology was reviewed to confirm WHO type 2 or 3 NPC. Patients were staged using the 1997 International Union Against Cancer (UICC) criteria. Mean potential follow-up time was 9.6 years (range, 1.0-18.5 years) There were 158 patients: 86 Asian and 72 non-Asian. Stage groupings were: I--12 patients; II--32 patients; III--59 patients; and IV--55 patients. A staging computerized tomography was performed in 121 patients, and 53 (34%) also had a staging magnetic resonance imaging (MRI). The Asian patients had significantly more women, more patients aged <45, and more with performance status 0 than the non-Asians. Other putative prognostic factors were not significantly different between the groups. The 5-year rates for freedom from local recurrence (FLR), failure-free survival (FFS), and overall survival (OS) for Asian and non-Asian patients were 74% vs. 82%, 61% vs. 55%, and 75% vs. 63%, respectively. Corresponding 10-year figures were: 62% vs. 82%, 43% vs. 48%, and 58% vs. 49%, respectively. Multifactor analysis showed stage and the use of MRI for staging to be significant prognostic factors for all three endpoints. Age was also significant for FFS and OS. There were no significant differences in FFS or OS between Asian and non-Asian patients. However, the FLR interval was significantly worse in the Asian group (hazard ratio [HR], 2.37; 95% confidence interval [CI], 1.11-5.06), whereas duration of freedom from distant metastasis tended to be better (HR, 0.71; 95% CI, 0.33-1.53). Although this study provides no evidence that race is an independent prognostic factor for overall survival in patients with WHO 2/3 NPC, it does suggest that relapse patterns may vary, with a higher rate of late primary failures (offset by a lower rate of distant failure) in the Asian population. Further confirmatory studies with larger patient cohorts are indicated.

Is the 1997 AJCC staging system for nasopharyngeal carcinoma prognostically useful for Chinese patient populations?

Purpose: The 5th edition of the American Joint Committee on Cancer (AJCC) staging manual defines new rules for classifying nasopharyngeal carcinoma (NPC). The study was conducted to assess its effectiveness in predicting the prognosis for Chinese patient populations. Methods and Materials: Between June 1993 and June 1994, 621 consecutively admitted patients with nondisseminated NPC were treated with definitive-intent radiation therapy alone. All had computed tomography of the nasopharynx, skull base, and the upper neck. A computer database containing all information for staging was formed on presentation. The extent of disease of each patient was restaged according to the 1997 AJCC system. Results: Of the 621 patients, The 5-year overall survival (OS) rate was 60%. The 1997 AJCC system creates subgroups (Stages I to IV) that are assigned to 38 (6.1%), 270 (43.5%), 157 (25.3%), and 156 (25.1%) patients, respectively. The incidence of parapharyngeal extension was 74.1% (460/621). Of these patients (460) with parapharyngeal extension, 310 (67.4%) patients were classified as T2b disease. The 1997 AJCC system showed highly significant differences between the overall stages for both OS and relapse-free survival (RFS). The 1997 AJCC T classifications showed significant correlation with local failure, and N classification was accurate in predicting FDM. Multivariate analysis showed that paraoropharyngeal involvement was an independently significant prognostic factor for OS, freedom from local recurrence (FLR), and freedom form distant metastasis (FDM). Conclusion: The 1997 AJCC staging system for NPC is prognostically useful for Chinese patient populations. We proposed that subdivision of parapharyngeal extension should be included in future revisions of the staging system.

Factors predicting patterns of recurrence after resection of N1 non-small cell lung carcinoma

Background. Although irradiation and chemotherapy are unproved adjuvant treatments for completely resected N1 non–small cell lung carcinoma, previous studies may have been diluted by the inclusion of low-risk patients. Risk factors in this situation, however, are not yet well defined. Methods. One hundred seven consecutive patients with complete resection of N1 disease who received no other therapy were studied to identify factors independently predicting the risk of freedom from local recurrence (FFLR), freedom from distant metastasis (FFDM), and overall survival (OS). Results. Twelve factors were assessed for a potential prognostic relationship with FFLR, FFDM, and OS. Regression analyses revealed that the factors independently associated with an improved outcome were positive bronchoscopic findings (FFLR, p = 0.005), a greater number of dissected N1 nodes (FFDM, p = 0.02), and a lesser T stage (OS, p = 0.01). Classification and regression tree analyses were then used to separate the patients into risk groups. Conclusions. Although these results require corroboration in further studies, they may aid the design of trials examining therapies used to decrease rates of local recurrence or distant metastasis.

Patients with stage I non-small cell lung carcinoma at postoperative risk for local recurrence, distant metastasis, and death: implications related to the design of clinical trials

Purpose: Patients with pathologically staged American Joint Committee on Cancer stage I (T1 N0 or T2 N0) non-small cell lung cancer have a favorable prognosis after complete surgical resection compared with patients with more advanced stages. Benefits of adjuvant therapy in this setting are unproved. However, there may be subgroups of patients with stage I disease at high enough risk for local recurrence to prompt consideration of adjuvant or neoadjuvant radiation therapy. Likewise, there may be subgroups of patients at high enough risk for distant metastasis to justify the evaluation of chemotherapy.Methods and Materials: From 1987 through 1990, 370 patients undergoing gross total resection of non-small cell lung cancer had stage I disease and received no chemotherapy or radiation therapy as part of their primary treatment. These patients were the subject of a retrospective review to separate patients into high-, intermediate-, and low-risk groups with respect to freedom from local recurrence (FFLR), freedom from distant metastasis (FFDM), and overall survival by using a regression tree analysis.Results: The 5-year rates of FFLR, FFDM, and survival were 85%, 83%, and 66%, respectively. Regression analyses revealed that the factors independently predicting for a poorer FFLR rate included fewer than 15 lymph nodes dissected and pathologically evaluated (p = 0.002) and the presence of a T2 tumor (p = 0.04). Factors independently predicting for a poorer FFDM rate included a maximal dimension greater than 5 cm (p = 0.02) and nonsquamous histology (p = 0.03). Factors independently predicting for a poorer survival rate included fewer than 15 lymph nodes dissected and pathologically evaluated (p = 0.001) and a maximal dimension greater than 3 cm (p = 0.003). Regression tree analyses were used to separate patients into risk groups.Conclusion: Incorporating the aforementioned factors into regression tree analyses, three risk groups were identified with respect to FFLR. Two each were identified for FFDM and for survival. For each of these three end-points, the differences in outcomes for each risk group were found to be both statistically and clinically significant. These risk groups may be useful in the future design of phase III trials evaluating the use of adjuvant chemotherapy and radiation therapy in the stage I setting.