N2-N3 Disease Research Articles

Postmastectomy internal mammary node radiation in women with breast cancer: a long-term follow-up study

AbstractBackgroundTo observe the impact of internal mammary node irradiation (IMNI) on disease-free survival (DFS) and overall survival (OS) in postmastectomy women with breast cancer.Materials and methodsBetween 1978 and 1996, 153 women with stage II–III breast cancer were treated with postmastectomy radiation therapy (RT) with IMNI. Their clinical, pathological and treatment characteristics were matched with 166 patients without IMNI. The RT dose was 35 Gy to the chest wall and 40 Gy to the supraclavicular fossa and IMN in 15 fractions over 3 weeks with photons. All patients were planned with two-dimensional technique. Adjuvant chemotherapy was administered to 41% and endocrine therapy to 52% of the patients. Symptomatic patients were further assessed for late pulmonary and late cardiac effects.ResultsThe median follow-up period was 203 months (range, 182–224), and the median age was 44 years (range 20–73 years). The IMNI group had significantly more right-sided and inner/central quadrant tumours. Other characteristics were comparable between both the groups. DFS at 15 years with and without IMNI was 64 and 49%, respectively (p=0·0001). On multivariate analysis, IMNI was an independent, positive predictor of DFS [hazard ratio (HR), 2·89;p=0·0001]. Benefit of IMNI on DFS was more apparent in inner/central tumours [HR, 1·48; 95% confidence interval (CI), 1·02–2·88], N2–N3 patients (HR, 1·44; 95% CI, 1·09–2·10) and in those who received chemotherapy (HR, 1·70; 95% CI, 1·07–2·71). OS at 15 years with and without IMNI was 68 and 54%, respectively (p=0·0001). Late pulmonary toxicity was 1·5 versus 1% with and without IMNI, respectively. Late cardiac toxicity was 2·6 versus 1·8% with and without IMNI, respectively.ConclusionsIMNI significantly improved DFS and OS in postmastectomy breast cancer patients. Benefit of IMNI was seen in patients with central/inner tumours and N2–N3 disease. Late cardiopulmonary toxicities were comparable between the two groups.

Clinical Outcome among Nasopharyngeal Cancer Patients in a Multi-Ethnic Society in Singapore.

BackgroundNasopharyngeal cancer (NPC) is endemic among Chinese populations in Southeast Asia. However, the outcomes of non-Chinese NPC patients in Singapore are not well reported.AimTo determine if non-Chinese NPC patients have a different prognosis and examine the clinical outcomes of NPC patients in a multi-ethnic society.MethodsRetrospective chart review of 558 NPC patients treated at a single academic tertiary hospital from 2002 to 2012. Survival and recurrence rates were analysed and predictive factors identified using the Kaplan-Meier method and Cox regression model.ResultsOur cohort comprised 409 males (73.3%) and 149 females (26.7%) with a median age of 52 years. There were 476 Chinese (85.3%), 57 Malays (10.2%), and 25 of other ethnic groups (4.5%). Non-Chinese patients were more likely to be associated with advanced nodal disease at initial presentation (p = 0.049), compared with the Chinese. However, there were no statistical differences in their overall survival (OS) or disease specific survival (DSS) (p = 0.934 and p = 0.857 respectively). The 3-year and 5-year cohort OS and DSS rates were 79.3%, 70.7%, and 83.2%, 77.4% respectively. Advanced age (p<0.001), N2 disease (p = 0.036), N3 disease (p<0.001), and metastatic disease (p<0.001) at presentation were independently associated with poor overall survival. N2 disease (p = 0.032), N3 disease (p<0.001) and metastatic disease (p<0.001) were also independently associated with poor DSS. No predictive factors were associated with loco-regional recurrence after definitive treatment. Advanced age (p = 0.044), N2 disease (p = 0.033) and N3 disease (p<0.001) were independently associated with distant relapse.ConclusionIn a multi-ethnic society in Singapore, non-Chinese are more likely to present with advanced nodal disease. This however did not translate into poorer survival outcomes. Older patients with N2 or N3 disease are associated with a higher risk of distant relapse and poor overall survival.

Is maximum primary tumor diameter still a prognostic factor in patients with nasopharyngeal carcinoma treated using intensity-modulated radiotherapy?

BackgroundIntensity-modulated radiation therapy (IMRT) has represented a technical milestone that has facilitated the clinical implementation. The purpose of this study was to evaluate the prognostic value of maximum primary tumor diameter (MPTD) in patients with nasopharyngeal carcinoma (NPC) treated using IMRT.MethodsFive-hundred and sixty-six patients with non-metastatic, histologically-confirmed NPC were retrospectively reviewed. MPTD was measured using magnetic resonance imaging (MRI). All patients were treated using IMRT; 87.5% (456/521) of patients with Stage T3-T4/N1-N3 disease also received cisplatin-based chemotherapy. Receiver operating characteristic (ROC) curves were used to identify the optimal MPTD cut-off point and examine the prognostic value of combining MPTD with the current T classification criteria.ResultsMedian follow-up for all patients was 36 months (range, 1–52 months). The 3-year overall survival (OS), failure-free survival (FFS), distant metastasis-free survival (DMFS), and local relapse-free survival (LRFS) rates for patients with a MPTD ≤41 vs. >41 mm were 96.1% vs. 85.4%, 93.7% vs. 74.7%, 96.1% vs. 79.7%, and 98.1% vs. 92.9%, respectively (all P < 0.05). In multivariate analysis, MPTD was an independent prognostic factor for OS, FFS, DMFS and LRFS in all patients (all P < 0.05). Among stage T3-T4 patients, the 3-year OS, FFS, DMFS, and LRFS rates for patients with a MPTD ≤41 vs. >41 mm were 96.9% vs. 84.5%, 95.4% vs. 73.5%, 96.1% vs. 79.2%, and 99.3% vs. 92.6%, respectively (all P < 0.05). In multivariate analysis, MPTD was also an independent prognostic factor for OS, FFS and DMFS in stage T3-T4 patients (all P < 0.05), and the difference in LRFS was almost statistically significant (P = 0.05). ROC curves verified that inclusion of MPTD improved the predictive value of the current T classification criteria (P < 0.001).ConclusionsMPTD was an independent prognostic factor in patients with NPC treated using IMRT, and significantly improved the prognostic value of the current T classification criteria for NPC.

Nodal Stage of Surgically Resected Non-Small Cell Lung Cancer and Its Effect on Recurrence Patterns and Overall Survival

Current National Comprehensive Cancer Network guidelines recommend postoperative radiation therapy (PORT) for patients with resected non-small cell lung cancer (NSCLC) with N2 involvement. We investigated the relationship between nodal stage and local-regional recurrence (LR), distant recurrence (DR) and overall survival (OS) for patients having an R0 resection. A multi-institutional database of consecutive patients undergoing R0 resection for stage I-IIIA NSCLC from 1995 to 2008 was used. Patients receiving any radiation therapy before relapse were excluded. A total of 1241, 202, and 125 patients were identified with N0, N1, and N2 involvement, respectively; 161 patients received chemotherapy. Cumulative incidence rates were calculated for LR and DR as first sites of failure, and Kaplan-Meier estimates were made for OS. Competing risk analysis and proportional hazards models were used to examine LR, DR, and OS. Independent variables included age, sex, surgical procedure, extent of lymph node sampling, histology, lymphatic or vascular invasion, tumor size, tumor grade, chemotherapy, nodal stage, and visceral pleural invasion. The median follow-up time was 28.7 months. Patients with N1 or N2 nodal stage had rates of LR similar to those of patients with N0 disease, but were at significantly increased risk for both DR (N1, hazard ratio [HR] = 1.84, 95% confidence interval [CI]: 1.30-2.59; P=.001; N2, HR = 2.32, 95% CI: 1.55-3.48; P<.001) and death (N1, HR = 1.46, 95% CI: 1.18-1.81; P<.001; N2, HR = 2.33, 95% CI: 1.78-3.04; P<.001). LR was associated with squamous histology, visceral pleural involvement, tumor size, age, wedge resection, and segmentectomy. The most frequent site of LR was the mediastinum. Our investigation demonstrated that nodal stage is directly associated with DR and OS but not with LR. Thus, even some patients with, N0-N1 disease are at relatively high risk of local recurrence. Prospective identification of risk factors for local recurrence may aid in selecting an appropriate population for further study of postoperative radiation therapy.

Testicular tumors: what radiologists need to know--differential diagnosis, staging, and management.

Cryptorchidism, family history, and infertility are risk factors for testicular cancer. Most testicular cancers occur in young men aged 18-35 years, and seminoma is the most common cell type. Testicular tumors are usually diagnosed at ultrasonography (US) and are staged at computed tomography (CT) or magnetic resonance (MR) imaging. At US, testicular tumors usually appear as a solid intratesticular mass. Because the differential diagnosis includes infarct and infection, correlation with patient history and symptoms is important. At staging CT or MR imaging, retroperitoneal lymph nodes are considered regional lymph nodes, and the greatest nodal diameter is used to distinguish among N1-N3 disease. The right testicular vein drains into the inferior vena cava, and the left testicular vein drains into the left renal vein. Because of venous and lymphatic drainage pathways, retroperitoneal lymph nodes are the initial landing station for testicular cancers. Enlarged lymph nodes in the supraclavicular region, chest, and pelvis are considered distant metastases. Testicular cancer is initially treated with orchiectomy. The patient may then undergo active surveillance, chemotherapy, radiation therapy, or retroperitoneal lymph node resection, depending primarily on the clinical stage. Radiologists play an important role in initial diagnosis, staging, and imaging surveillance of testicular malignancies.

Tumor Volume of Resectable Adenocarcinoma of the Esophagogastric Junction at Multidetector CT: Association with Regional Lymph Node Metastasis and N Stage

To determine whether the volume of resectable adenocarcinoma of the esophagogastric junction (AEG) measured at multidetector computed tomography (CT) is associated with regional lymph node metastasis and N stage. The study was approved by the institutional ethics committee, and written informed consent was obtained from each participant. Two hundred sixteen patients with resectable AEG prospectively underwent contrast material-enhanced thoracoabdominal multidetector CT less than 2 weeks before curative resection. Gross tumor volume was retrospectively measured on CT scans. Univariate and multivariate analyses were performed to identify whether gross tumor volume is associated with regional lymph node metastasis. The Mann-Whitney U test was performed to compare gross tumor volume among N stages, with Bonferroni correction for multigroup comparisons. Receiver operating characteristic analysis was performed to determine if gross tumor volume could help classify N stage. Univariate analysis showed that gross tumor volume is associated with regional lymph node metastasis (P < .0001). Multivariate analysis revealed that gross tumor volume is an independent risk factor of lymph node metastasis (P = .023, odds ratio = 2.791). The Mann-Whitney U test showed that gross tumor volume could help differentiate between stage N0 and stages N1-N2 or N1-N3 disease and between stages N1-N2 and stage N3 disease (P < .0001 for all). In patients with stage T1-T3 AEG, gross tumor volume could help differentiate between stage N0 and stages N1-N2 (cutoff, 15.23 cm(3)) or N1-N3 (cutoff, 17.16 cm(3)) disease and between stages N1-N2 and stage N3 disease (cutoff, 33.96 cm(3)). In patients with stage T3 AEG, gross tumor volume could help differentiate stage N0 from stages N1-N2 (cutoff, 18.41 cm(3)) or N1-N3 (cutoff, 19.30 cm(3)) disease and stages N1-N2 from stage N3 disease (cutoff, 33.96 cm(3)). Gross tumor volume of AEG measured with multidetector CT is associated with regional lymph node metastasis and N stage.

Risk factors for local and regional recurrence in patients with resected N0–N1 non-small-cell lung cancer, with implications for patient selection for adjuvant radiation therapy

The purpose of this study was to evaluate the actuarial risk of local and regional failure in patients with completely resected non-small-cell lung cancer (NSCLC), and to assess surgical and pathological factors affecting this risk. Between January 1998 and December 2009, 1402 consecutive stage I-III (N0-N1) NSCLC patients underwent complete resection without adjuvant radiation therapy. The median follow-up was 42 months. Local-regional recurrence was identified in 9% of patients, with local failure alone in 3% of patients, regional failure alone in 4% of patients, and both local and regional failure simultaneously in 2% of patients. Patients who had local failure were found to be at increased risk of mortality. By multivariate analyses, three variables were shown to be independently significant risk factors for local [surgical procedure (single/multiple wedges+segmentectomy versus lobectomy+bilobectomy+pneumonectomy), tumor size>2.7 cm, and visceral pleural invasion] and regional (pathologic N1 stage, visceral pleural invasion, and lymphovascular space invasion, LVI) recurrence, respectively. Patients with N0-N1 disease have low rates of locoregional recurrence after surgical resection. However, several prognostic factors can be identified that increase this risk and identify patients who may benefit from adjuvant treatment.

18F-FDG PET/CT in Staging Patients with Locally Advanced or Inflammatory Breast Cancer: Comparison to Conventional Staging

The prognosis of patients with locally advanced breast cancer (LABC) remains poor. We prospectively investigated the impact of (18)F-FDG PET/CT at initial staging in this clinical setting and compared PET/CT performance with that of conventional distant work-up. During 60 mo, consecutive patients with LABC (clinical T4 or N2-N3 disease) underwent (18)F-FDG PET/CT. The yield was assessed in the whole group and separately for noninflammatory and inflammatory cancer. The performance of PET/CT was compared with that of a conventional staging approach including bone scanning, chest radiography, or dedicated CT and abdominopelvic sonography or contrast-enhanced CT. 117 patients with inflammatory (n = 35) or noninflammatory (n = 82) LABC were included. (18)F-FDG PET/CT confirmed N3 nodal involvement in stage IIIC patients and revealed unsuspected N3 nodes (infraclavicular, supraclavicular, or internal mammary) in 32 additional patients. Distant metastases were visualized on PET/CT in 43 patients (46% of patients with inflammatory carcinoma and 33% of those with noninflammatory LABC). Overall, (18)F-FDG PET/CT changed the clinical stage in 61 patients (52%). Unguided conventional imaging detected metastases in only 28 of the 43 patients classified M1 with PET/CT (65%). (18)F-FDG PET/CT outperformed conventional imaging for bone metastases, distant lymph nodes, and liver metastases, whereas CT was more sensitive for lung metastases. The accuracy in diagnosing bone lesions was 89.7% for planar bone scanning versus 98.3% for (18)F-FDG PET/CT. The accuracy in diagnosing lung metastases was 98.3% for dedicated CT versus 97.4% for (18)F-FDG PET/CT. (18)F-FDG PET/CT had the advantage of allowing chest, abdomen and bone to be examined in a single session. Almost all distant lesions detected by conventional imaging were depicted with PET/CT, which also showed additional lesions.

High Negative Predictive Value of FDG-PET/CT in Assessment of Tumor Response Following Radiation Treatment for Head-and-Neck Carcinomas: Long-term update

High Negative Predictive Value of FDG-PET/CT in Assessment of Tumor Response Following Radiation Treatment for Head-and-Neck Carcinomas: Long-term update

Prognosis and Patterns of Failure of Patients With Non-small Cell Lung Cancer Having Hypermetabolic Mediastinal Lymph Nodes on Preoperative PET but N0-N1 Disease on Pathological Analysis

Prognosis and Patterns of Failure of Patients With Non-small Cell Lung Cancer Having Hypermetabolic Mediastinal Lymph Nodes on Preoperative PET but N0-N1 Disease on Pathological Analysis

Definitive radiotherapy for squamous cell carcinoma of the pyriform sinus

Background and purposeTo report the long-term results after definitive radiotherapy (RT) for pyriform sinus squamous cell carcinoma (SCC). Material and methodsThe data concerning all patients treated for pyriform sinus SCC with RT with a curative intent between 1990 and 2006 were reviewed. ResultsA total of 249 patients were included. The median follow-up is 6.5years. Overall 123 patients had relapsed. For the entire population, the 5-year local control, regional control, freedom-from-distant metastasis, and overall survival rate were 68%, 69%, 78% and 38%, respectively. The 5-year local control rate for the 107 T1–T2 tumors was 85% (95% confidence interval (CI): 75–91). N stage was the main risk factor for the development of distant metastases, with a hazard ratio of 8.9 (95% CI: 2.1–39) and 15.6 (95% CI: 3.6–67.8) for N2 and N3 patients respectively. For patients with N2–N3 disease, pre-RT neck dissection improved regional control but not overall survival. Moderate to severe late complications occurred in 50 patients (28% of the patients without local relapse). ConclusionA high local control rate can be achieved when treating T1–T2 hypopharynx cancers with definitive radiotherapy. The high rate of nodal and distant relapses among patients with N2–N3 disease warrants intensification of therapy.

Erlotinib and chemoradiation in patients with surgically resected locally advanced squamous cell carcinoma of the head and neck: a GICOR phase I trial

Standard treatment of advanced squamous cell carcinoma of the head and neck (SCCHN) is concurrent chemoradiation. Erlotinib is an oral tyrosine kinase inhibitor of epidermal growth factor receptor, which has shown activity in SCCHN. Phase I study aims to determine the maximum tolerated dose and dose-limiting toxicity (DLT) of adding erlotinib to chemoradiation therapy in patients with surgically resected locally advanced SCCHN. Inclusion criteria--SCCHN patients with T3 or T4 primary lesion (except T3N0 with negative resection margins); pathologic N2-N3 disease; poor prognostic findings; age 18-70 years; Eastern Cooperative Oncology Group performance status of zero to one; no evidence of metastasis; adequate organic function and written informed consent. Study design--dose-escalating phase I study with three cohorts of three to six patients each that received increasing doses of erlotinib (100-150 mg/day p.o.) and cisplatin (30-40 mg/m(2) i.v., day 1) for 7 weeks. Radiotherapy--standard regimen of 1.8 Gy daily (5 fractions/week) to a maximum total dose of 63 Gy in 7 weeks. Thirteen male (median age: 57 years) were enrolled. Overall, the regimen was well tolerated. Two of three patients treated at dose level III (erlotinib: 150 mg/day; cisplatin: 40 mg/m(2)) developed DLT consisting of grade 3 infection and grade 3 mucositis. Other toxic effects included diarrhea, asthenia, and rash. Recommended dose for additional studies: erlotinib 150 mg/day p.o.; cisplatin 30 mg/m(2)/week i.v. Erlotinib can be safely combined with chemoradiation without requiring dose reduction of chemo- or radiotherapy in this postsurgical population.

Pathological Status of Mediastinal Lymph Nodes after Preoperative Concurrent Chemoradiotherapy Determines Prognosis in Patients with Non-Small Cell Lung Cancer

The benefits of preoperative chemoradiotherapy for advanced nonsmall cell lung cancer (NSCLC) remain controversial. To evaluate prognostic indicators of clinical N2 NSCLC patients treated with concurrent chemotherapy followed by pulmonary resection, we performed a retrospective study. We retrospectively investigated 52 patients with pathologically proven N2 NSCLC who underwent concurrent chemoradiotherapy before pulmonary resection. Each received 2 cycles of cisplatin-vinca alkaloid-based chemotherapy every 4 weeks. Radiotherapy, directed at the tumor and mediastinal nodes, was started on day 2 at a median dose of 44 Gy. A thoracotomy was performed 6 to 8 weeks after completion of chemoradiotherapy. The overall 5-year survival rate for the 52 patients was 38%. Complete pathological response by the tumor was found in 11 (21%). Down-staging of nodal stage occurred in 29 patients, (56%) and overall survival was better in those with lower pathological N status. The 5-year survival rate was 58% for pathological N0-N1 disease and 0% for N2 disease. While the response to induction therapy by the primary tumor was correlated with postoperative nodal stage, multivariate analysis revealed postoperative nodal stage as an independent prognostic factor. Pathological status of mediastinal lymph nodes in response to preoperative concurrent chemoradiotherapy determined prognosis in our patients.

Individualised isotoxic accelerated radiotherapy and chemotherapy are associated with improved long-term survival of patients with stage III NSCLC: A prospective population-based study

BackgroundIndividualised, isotoxic, accelerated radiotherapy (INDAR) allows the delivery of high biological radiation doses, but the long-term survival associated with this approach is unknown. MethodsPatients with stage III NSCLC in the Netherlands Cancer Registry/Limburg from January 1, 2002 to December 31, 2008 were included. ResultsPatients (1002) with stage III NSCLC were diagnosed, of which 938 had T4 and/or N2–N3 disease. Patients treated with curative intent were staged with FDG-PET scans and a contrast-enhanced CT or an MRI of the brain. There were no shifts over time in the patient or tumour characteristics at diagnosis. The number of stage III NSCLC patients remained stable over time, but the proportion treated with palliative intent decreased from 47% in 2002 to 37% in 2008, and the percentage treated with chemo-radiation (RT) increased from 24.6% in 2002 to 47.8% in 2008 (p<0.001). The proportion of surgical patients remained below 5%. Sequential chemotherapy and conventional RT resulted in a median and a 5-year survival of 17.5months and 8.4%, respectively, whereas with sequential chemotherapy and INDAR this was 23.6months and 31%, respectively (p<0.001). Concurrent chemotherapy and INDAR was associated with a median and 2-year survival that was not reached and 66.7%, respectively (p=0.004). ConclusionsThe proportion of patients treated with a curative intention with chemo-RT has increased markedly over time of observation. INDAR is associated with longer survival when compared to standard dose RT alone given with or without chemotherapy.

Non–Small Cell Lung Cancer: Prognostic Importance of Positive FDG PET Findings in the Mediastinum for Patients with N0–N1 Disease at Pathologic Analysis

To assess the prognostic implications of mediastinal positron emission tomographic (PET) findings in patients undergoing curative resection of non-small cell lung cancer (NSCLC) who have histologically negative mediastinal lymph nodes (LNs), with the hypothesis that positive findings at PET are prognostic even in patients with negative histologic findings in the LNs. Records of patients with a preoperative PET undergoing curative surgery, without adjuvant radiation, for pathologic T1-3N0-1 NSCLC at the University of North Carolina between 2000 and 2006 were reviewed as an institutional review board-approved HIPAA-compliant retrospective study. Ninety patients were evaluable (all histologically negative in mediastinum; 44 with both mediastinoscopy and surgery); 13 patients had positive mediastinal PET findings, and 77 had negative mediastinal PET findings. Local-regional and distant failure rates in patients with and those without mediastinal abnormalities at preoperative PET were compared by using logistic regression and log-rank tests. Median follow-up was 54.3 months (range, 1-99 months). There were higher rates of local-regional (P = .001) and distant (P < .001) failure as well as death (P = .001) in patients with postive PET findings than in patients with negative findings. In multivariable analysis (adjusting for other prognostic factors), positive PET findings in the mediastinum remained prognostic for distant failure (P < .001, hazard ratio = 6.9) and were marginally prognostic for local-regional failure (P = .093, hazard ratio = 1.9). Positive findings at preoperative PET in the mediastinum appear to have prognostic implications despite the mediastinal LNs being histologically negative. The high rate of local-regional and distant failure suggests that postoperative radiation therapy and/or chemotherapy may be particularly helpful in patients with positive mediastinal findings at preoperative PET.

Non–Small Cell Lung Cancer: Prognostic Importance of Positive FDG PET Findings in the Mediastinum for Patients with N0–N1 Disease at Pathologic Analysis

Non–Small Cell Lung Cancer: Prognostic Importance of Positive FDG PET Findings in the Mediastinum for Patients with N0–N1 Disease at Pathologic Analysis

Prognostic value of estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 in node positive breast cancer patients treated by mastectomy

To evaluate the prognostic value of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (Her-2) in node-positive breast cancer patients treated by mastectomy. The clinicopathological data of 835 breast cancer patients treated by mastectomy from January 2000 to December 2004 were retrospectively analyzed. All had positive axillary nodes without distant metastases and with the immunohistochemistry staining of ER, PR and Her-2 available. 764 (91.5%) patients received anthracycline- and/or taxanes-based chemotherapy. 464 (55.6%) patients received hormonal therapy. Eight (1%) patients received trastuzumab. Postmastectomy radiotherapy were given to 352 out of 437(80.5%)patients with T3-T4 and/or N2-N3 disease and 68 out of 398(20.9%)patients with T1-2N1 disease. Patients were classified into 4 subgroups according to the status of hormone receptors (ER and PR, Rec) and Her-2: Rec(-)/Her-2(-) (triple negative), Rec(-)/Her-2(+), Rec(+)/Her-2(+) and Rec(+)/Her-2(-). End points were isolated locoregional recurrence (LRR), distant metastases (DM), disease-free survival (DFS) and overall survival (OS). 141 (16.9%) patients were Rec(-)/Her-2(-), 99 (11.9%) Rec(-)/Her-2(+), 157 (18.8%) Rec(+)/Her-2(+) and 438 (52.5%) Rec(+)/Her-2(-). Patients with Rec(+)/Her-2(-) breast cancer had a significantly lower 5-year LRR rate than others (6.2% vs. 12.9%, P = 0.004). Compared with patients with Rec(+) breast cancer, patients with Rec(-) breast cancer had significantly higher 5-year DM rate (26.4% vs. 19.7%, P = 0.0008), lower DFS rate (66.7% vs. 75.6%, P = 0.0001) and lower OS rate (71.4% vs. 84.2%, P = 0.0000). In multivariate analysis, Rec(+)/Her-2(-) was significantly associated with lower risk of LRR. Rec(-) was an independent prognostic factor for higher risk of DM, decreased DFS and OS. ER, PR and Her-2 are independent prognostic factors for locoregional recurrence and survival in node-positive breast cancer patients treated by mastectomy.

A phase I/II study of erlotinib in combination with chemoradiation in patients with surgically resected locally advanced squamous head and neck cancer (HNSCC).

TPS266 Background: Standard postoperative treatment for high-risk locally advanced HNSCC is concurrent chemoradiation (CRT). Despite innovative strategies, prognosis of these patients remains poor. Up to 90% of HNSCC overexpresses the EGF receptor. Erlotinib (e) is an oral tyrosine-kinase inhibitor of EGFR, with activity in HNSCC. The Spanish Group of Clinical Research in Radiation Oncology (GICOR) sponsors a multicenter non randomized phase I/II study evaluating the addition of E to CRT therapy of patients (pts) with surgically resected locally advanced HNSCC. Methods: The study comprises an early dose-escalating phase I, consisting on 3 cohorts of 3-6 pts each, with increasing doses of E (100-150 mg po qd) and cisplatin (C) (30-40 mg/m2, iv, d 1) for 7 weeks (w). Radiation therapy (RT) is delivered as a standard regimen of daily 1.8 Gy (5 fractions/w) to a maximum total dose of 63 Gy along 7 w. Pts should have diagnosis of HNSCC, with at least one of these criteria: T3 or T4 primary lesion (except T3N0 with negative resection margins), pathologic N2-N3 disease, and poor prognostic findings. Other criteria: age 18-70 y; life expectancy ≥ 12 w; PS 0-1; no evidence of metastasis; adequate organic function and written informed consent. The aim of the phase I is to define the maximum tolerated dose (MTD), as the dose level at which 2 of 3 or 3 of 6 pts develop a dose-limiting toxicity (DLT). DLT, in turn, is defined as any grade (g) 3-4 hematological or nonhematological clinically severe toxicity, including g 3-4 diarrhea, g 4 mucositis resulting in more than 2 w interruption of RT; g 3-4 mucositis complicated with a decrease ECOG PS; g 3-4 skin rash; or any clinically relevant toxicity resulting in interruption of treatment for more than 2 w. Phase I has been already completed, being a regimen of C 30 mg/m2 + E 150 mg/day the recommended dose for the phase II (Arias et al. J Clin Oncol 26: 2008, abstr. 6068). The primary objective of the phase II is to evaluate the progression-free survival (PFS) of pts treated at the recommended dose; secondary objectives locoregional PFS and overall survival. Planned sample size is 70 pts, and 32 have been enrolled since the beginning of the phase II (mid-2008). No significant financial relationships to disclose.

Place du curage ganglionnaire après chimioradiothérapie dans les carcinomes épidermoïdes des voies aérodigestives supérieures avec atteinte ganglionnaire initiale (nasopharynx exclu)

The optimal timing and extent of neck dissection in the context of chemoradiation for head and neck cancer remains controversial. For some institutions, it is uncertain whether neck dissection should still be performed upfront especially for cystic nodes. For others, neck dissection can be performed after chemoradiation and can be omitted for N1 disease as long as a complete response to chemoradiation is obtained. The question is debated for N2 and N3 disease even after a complete response as the correlation between radiological and clinical assessment and pathology may not be reliable. Response rates are greater than or equal to 60% and isolated neck failures are less than or equal to 10% with current chemoradiation protocols. Some therefore consider that systematic upfront or planned neck dissection would lead to greater than or equal to 50% unnecessary neck dissections for N2-N3 disease. Positron-emission tomography (PET) scanning to assess treatment response and have shown a very high negative predictive value of greater than or equal to 95% when using a standard uptake value of 3 for patients with a negative PET at four months after the completion of therapy. These data may support the practice of observing PET-negative necks. More evidence-based data are awaited to assess the need for neck dissection on PET. Selective neck dissection based on radiological assessment and peroperative findings and not exclusively on initial nodal stage may help to limit morbidity and to improve the quality of life without increasing the risk of neck failure. Adjuvant regional radiation boosts might be discussed on an individual basis for aggressive residual nodal disease with extracapsular spread and uncertain margins but evidence is missing. Medical treatments aiming at reducing the metastatic risk especially for N3 disease are to be evaluated.

Whole-Field Simultaneous Integrated-Boost Intensity-Modulated Radiotherapy for Patients With Nasopharyngeal Carcinoma

To retrospectively review the outcomes of our patients with newly diagnosed nondisseminated nasopharyngeal carcinoma treated with intensity-modulated radiotherapy using a whole-field simultaneous integrated-boost technique. A total of 175 patients treated with WF-SIB between mid-2004 and 2005 were eligible for study inclusion. The distribution of disease by stage was Stage IA in 10.9%, Stage IIA in 2.3%, Stage IIB in 21.7%, Stage III in 41.1%, Stage IVA in 14.9%, and Stage IVB in 9.1%. Of the 175 patients, 2 (1.2%), 10 (5.7%), and 163 (93.1%) had World Health Organization type I, II, and III histologic features, respectively. We prescribed 70 Gy, 60 Gy, and 54 Gy delivered in 33 fractions within 6.5 weeks at the periphery of three planning target volumes (PTV; PTV70, PTV60, and PTV54, respectively). Of the 175 patients, 46 with early T-stage disease received a brachytherapy boost, and 127 with advanced local or regional disease received chemotherapy. The median follow-up period was 34 months. The overall 3-year local failure-free survival, regional failure-free survival, distant failure-free survival, and overall survival rate was 93.6%, 93.3%, 86.6%, and 87.2%, respectively. Cox regression analysis showed Stage N2-N3 disease (p = .029) and PTV (p = .024) to be independent factors predicting a greater risk of distant failure and poor overall survival, respectively. Grade 3 acute mucositis/pharyngitis occurred in 23.4% of patients, and Stage T4 disease was the only significant predictor of mucositis/pharyngitis (p = .021). Whole-field simultaneous integrated-boost intensity-modulated radiotherapy with a dose >70 Gy achieved excellent locoregional control, without an excess incidence of severe, acute mucositis/pharyngitis, in the present study. Strategies for using such highly conformal treatment for patients with a large tumor and late N-stage disease are potential areas of investigation for future studies.