Primary Site Recurrence Research Articles

Prognostic factors and selection criteria in the retreatment of head and neck cancers

ObjectivesTo determine predictors of treatment selection, outcome, and survival, we examined a cohort of previously irradiated head and neck squamous cell carcinoma (HNSCC) patients. Materials and methodsWe retrospectively analyzed 100 patients at our institution who were treated for recurrent or second primary (RSP) HNSCC, focusing on subgroups receiving reirradiation (ReRT) alone and those undergoing surgical salvage (SS) with or without post-operative reirradiation therapy (POReRT). Logistic regression modeling was performed to identify factors predictive of retreatment modality. Cox regression modeling was used to determine prognostic factors for progression free survival (PFS) and overall survival (OS). ResultsReRT alone was less likely in current smokers and neck recurrences, with reirradiation more likely in primary site recurrences. POReRT was significantly more likely in patients with positive surgical margins (PSM), neck dissection, or organ dysfunction. POReRT omission negatively impacted PFS when PSM (HR: 8.894, 95% CI: 1.742–45.403) and perineural invasion (PNI) (HR: 3.391, 95% CI: 1.140–10.089) were present. Tracheostomy was associated with worse OS, but ReRT alone and POReRT improved OS. PSM correlated with worse OS, regardless of whether POReRT was given (HR: 14.260, 95% CI: 2.064–98.547). ConclusionThis analysis confirms known factors for predicting outcome and shows nonsmoking status and primary site recurrence as predictors for ReRT alone. POReRT for PSM and PNI improves PFS. Tracheostomy patients are more likely to have ReRT due to acute toxicity not limiting treatment and POReRT improves OS compared to surgery alone. The presence of PSM negatively impacts survival which cannot be overcome by POReRT.

The Role of Positron Emission Tomography/Computed Tomography Imaging in Head and Neck Cancer after Radical Chemoradiotherapy: a Single Institution Experience

AimsPositron emission tomography/computed tomography (PET/CT) is used to restage head and neck cancer 3 months after chemoradiotherapy. The purpose of this study was to determine the negative predictive value (NPV) of a scan reported as having no abnormal uptake and the positive predictive values (PPV) for different maximum standardised uptake value (SUVmax) thresholds. Materials and methodsPatients with squamous cell carcinoma of the oro-/hypopharynx/larynx (n = 206) were included. SUVmax and subsequent locoregional recurrence were documented. ResultsThe median SUVmax was 11.2 (range 4–33)/4.6 (range 2–30), respectively, in patients with/without definite primary site recurrence (P = 0.004). The median SUVmax was 4.4 (range 2.6–15.6)/3.1 (range 2.1–4.6), respectively, in patients with/without definite nodal recurrence (P = 0.003). The NPV for a scan reported as having no abnormal uptake was 92%. The PPV for the SUVmax thresholds 4, 6 and 8, respectively, were 53, 65 and 92% (primary site) and 93, 100 and 100% (nodes). ConclusionsThe NPV of PET/CT after chemoradiation is consistent with the literature and underlines the importance of PET/CT in restaging the primary site if salvage neck dissection is considered. The overall PPV of PET/CT remains low but is high for nodal SUVmax > 4. These data could be used to design risk-stratified follow-up schedules.

Primary Recurrence in the Lung is Related to Favorable Prognosis in Patients with Pancreatic Cancer and Postoperative Recurrence.

The pattern of recurrence affects the clinical outcome in tumor patients. However, the clinical significance of lung metastasis as the primary recurrence site after resection in patients with pancreatic cancer remains unclear. This study aimed to clarify the clinical significance of the primary recurrence site in patients with pancreatic cancer, in terms of prognosis and clinicopathological features. This retrospective cohort study included 220 patients with postoperative recurrence after pancreatectomy for pancreatic cancer and classified by primary site of recurrence. We focused on patients with lung metastasis as the primary recurrence and investigated its correlation with prognosis and clinicopathological factors. Twenty-four (11%) patients had lung metastasis as the primary recurrence. This recurrence pattern had the best prognosis among all recurrence patterns, including liver metastasis and local recurrence. Patients with lung metastasis as the primary recurrence had favorable overall survival and survival from the date of recurrence compared with patients with other primary recurrence sites in both univariate (P=0.0008 and P=0.0005) and multivariate analyses (P=0.0051 and P=0.0068). In terms of clinicopathological features of resected pancreatic tumors, lung metastasis as the primary recurrence was associated with lower tumor stage and histologic grade, and less vascular invasion and residual tumor volume than liver metastasis. Pancreatic cancer patients with lung metastasis as the primary recurrence after pancreatectomy have a better prognosis than those with other recurrence patterns.

Treatment of glottic cancer involving the anterior commissure by transoral CO(2) laser surgery

Objective: To study the clinical outcome of transoral CO(2) laser surgery for glottic cancer involving the anterior commissure. Methods: Thirty-two cases of glottic cancer involving the anterior commissure treated by transoral CO(2) laser surgery between March 2009 and December 2013 were retrospectively reviewed. Among these cases, 27 were T1bM0M0, 5 were T2N0M0. All cases were followed-up for more than 3 years. Results: All the 32 cases were successfully treated. Perioperative complications included injuries in the soft palate mucosa(13/32, 40.63%), loose incisors(3/32, 9.38%) and subcutaneous emphysema in the neck(2/32, 6.25%). During the follow-up period, granulation was found in all cases. Three cases had local recurrence. Two patients treated by a secondary transoral CO(2) laser surgery and the other case had total laryngectomy, all three cases were followed up for 5 years without recurrence. Two cases had regional recurrence but no primary site recurrence. One patient was treated by neck dissection, and followed up for 5 years without recurrence. The other patient died of supraclavicular and mediastinal lymph node metastasis and lung metastasis 40 months after operation. The overall 5-year survival rate was 90.6%. There was no significant difference in survival rate between T1bN0M0(92.6%) and T2N0M0(80.0%) (Log Rank χ(2)=0.788, P=0.375). The overall 5-year local regional control rate was 84.4%. In T1bN0M0 lesions, the 5-year local regional control rate was 92.6%, which was significantly higher than that in T2N0M0 lesions(40.0%) (Log Rank χ(2)=9.504, P=0.002). Conclusion: With appropriate surgical indication, detailed preoperative evaluation, good surgical skill, transoral CO(2) laser surgery may achieve satisfactory outcome in the treatment of glottic cancer involving the anterior commissure.

Seeing double: Trigeminal neurotropic melanoma as primary recurrence site, presenting as diplopia. (P5.180)

Seeing double: Trigeminal neurotropic melanoma as primary recurrence site, presenting as diplopia. (P5.180)

Clinical characteristics and risk factors analysis of lung metastasis from benign giant cell tumor of bone

Pulmonary metastasis of benign giant cell tumor of bone is very rare, and its biological behavior is difficult to predict. In the present study, we analyzed the clinical characteristics of and related risk factors for pulmonary metastasis from this tumor. Forty-six patients with lung metastasis were analyzed. In total, 60.9% of the primary tumors were located around the knee joint. The Campanacci stage of all tumors was stage 3. Surgery of the primary tumor included curettage in 37 patients, resection in 8, and amputation in 1. Local recurrence after the primary surgery occurred in 34 patients. The recurrence rate, Campanacci stage, and surgical method were significant risk factors for lung metastasis. The median postoperative metastasis times in the lower limbs, upper limbs, and axial skeleton were 20.1, 7.9, and 1.4 months, respectively (p=0.010). The median metastasis times in patients with and without recurrence were 13.7 and 43.2 months, respectively (p=0.018). Eighteen patients had unilateral metastasis and 28 had bilateral metastasis. Most lesions (n=38) were located in the peripheral lung. Nineteen patients received treatment, and 12 of them underwent tumor resection. The 5-year overall survival rate was 94.4%. This study showed that local recurrence, a high Campanacci stage, and curettage were possible high-risk factors for pulmonary metastasis. The primary lesion site and local recurrence may be related to the metastasis time. The survival rate of patients with pulmonary metastasis was high.

Predictive Value of Primary Tumor Site for Loco-regional Recurrence in Early Breast Cancer Patients with One to Three Positive Axillary Lymphadenophy.

Introduction: It remains controversial on high risks for early breast cancer patients with one to three axillary nodes after mastectomy who is predisposition to locoregional recurrence. The present study is to investigate the relationship between primary tumor site and loco-regional recurrence (LRR) and explore the predictive value of clinicopathological characteristics in LRR for early breast cancer patients with one to three positive axillary lymph nodes after mastectomy.Methods: We reviewed the clinical data of 656 consecutively diagnosed patients with pT1-2N1M0 breast cancer who were treated in Sun Yat-sen University Cancer Center with radical operation without postoperative radiotherapy between March 1998 and December 2010. The primary tumor sites included outer quadrant in 455 patients (69.36%), inner quadrant in 156 patients (23.78%)and central quadrant in 45 patients (6.86%). LRR and LRR-free survival (LRFS) in combination with clinical and pathological features were analyzed to screen out patients with higher risk of LRR.Results: The median follow-up time was 64.9 months. The 5-, 10-year LRR for the cohort was 8.6% and 12.9%, respectively; the 5-, 10-year LRFS was 86.2% and 76.4%, respectively. Multivariate analyses showed that age of ≤35 years, inner quadrant tumor and non-luminal subtype were independent risk factors for LRR and LRFS. Patients with primary tumor in inner quadrant showed higher LRR and poorer LRFS when risk factors are ≥2 than those with tumors in other sites.Conclusions: Inner quadrant tumor was an independent predictor for LRR and LRFS in patients with early breast cancer and one to three positive axillary lymph nodes, which would be more accurate in combination with other prognostic indexes including patients' age, pathological T stage, Ki67 status, molecular subtypes.

Leptomeningeal carcinomatosis as the primary presentation of relapse in breast cancer.

Leptomeningeal metastasis (LM) is an uncommon presentation of relapse in breast cancer, which is associated with poor clinical outcomes and poor prognosis. Notably, LM most commonly occurs in breast cancer. The aim of the present review was to investigate the occurrence of LM as the primary presentation of relapse following remission in breast cancer patients and to determine whether specific histological subtypes are predisposed to meningeal metastases. In addition, the present review evaluated whether patients presenting with LM as the primary site of relapse exhibit differences in survival when compared with patients exhibiting metastasis to other sites. Cross-sectional studies have demonstrated that LM is commonly associated with other sites of distant metastasis including lung, liver and bone metastases. The histological breast cancer subtype most commonly associated with LM was invasive lobular carcinoma, while triple-negative breast cancer patients appear to be predisposed to the development of LM when considering the overall prevalence of histological breast cancer subtypes. At present, data regarding LM as the primary site of relapse are limited due to its rarity as the first site of metastasis in breast cancer. Case-controlled studies are required to investigate the incidence of LM as the primary site of recurrence in breast cancer patients as this would enable treatment standardization and identification of prognostic factors for improved survival.

Surveillance imaging and radiation exposure in the detection of relapsed neuroblastoma.

More than half of children with high-risk neuroblastoma (NB) will experience recurrence. Radiologic imaging is used for initial staging and during therapy to assess response. However, the role of surveillance imaging in the detection of relapse has not been well studied. Surveillance potentially results in high cumulative exposure to ionizing radiation, which may be associated with an increased risk of developing second malignancies. We reviewed NB cases at our institution between 2000 and 2011. We calculated radiation exposure due to imaging (during diagnosis, treatment, and posttherapy surveillance) using cumulative effective dose (CED) estimates and determined whether cross-sectional imaging identified recurrences. Fifty of 183 patients with NB experienced a recurrence. The median time from diagnosis to relapse was 1.20 years (range: 0.18-6.66 years). Most patients had evidence of metastases and only 4 of 50 patients presented with isolated primary tumor site recurrences. The mean CED prior to relapse was 125.2 mSv (range: 24.5-259.7), 64% of which was from computed tomography (CT) scans. Thirty-seven of 50 patients had clinically evident or measurable disease detected by X-ray (XR), ultrasound (US), or urinary catecholamines (UCats), and the addition of metaiodobenzylguanidine (MIBG) scans identified eight additional recurrences. Thus, cross-sectional imaging (CT/MRI, where MRI is magnetic resonance imaging) was only required to identify 10% (5/50) of cases. Relapsed disease was detected in most patients by symptoms/exam, MIBG scan, UCats, and/or XR/US, supporting reduced use of CT imaging in posttherapy surveillance, thereby decreasing cumulative radiation dose. Refinement of surveillance imaging may be further guided by risk stratification, disease sites, and potentially biomolecular markers.

Definitive chemoradiotherapy in Stage III nonsmall cell lung cancer: Turkey experience.

Concurrent chemoradiotherapy (CRT) is the standard therapy for patients with unresectable Stage III nonsmall cell lung cancer (NSCLC). The aim of this study was to assess the efficacy and safety of concurrent CRT in unresectable Stage III NSCLC in Turkey. The study included 82 patients with histologically proven unresectable Stage III NSCLC, Eastern Cooperative Oncology Group performance status 0-1, who received concurrent CRT in two different referral centers. Treatment consisted of two cycles of cisplatin at 50 mg/m 2 on days 1, 8, 29, and 36 and etoposide 50 mg/m 2 between days 1 and 5, 29-33 and concurrent radiotherapy administered once daily, 1.8-2.0 Gy per fraction, at a total dose of 60-66 Gy. The stages of the patients were Stage IIIA in 39 (47.5%) and IIIB in 43 (52.5%) patients. Complete and partial responses were achieved in 15 (18.2%) and 31 (37.8%) of the patients, respectively. Twenty-eight (34.2%) patients had stable disease and 8 (9.8) had progressive disease. Forty-one (50%) patients recurred during follow-up. The primary site of recurrence was as distant metastasis in 19 (23.2%) patients. Median overall survival (OS) was 20 months (95% confidence interval; 12.9-27.09 months), 3 and 4 years survivals were 27.9% and 20.9%, respectively. Median progression-free survival (PFS) was 9 months, 3 and 4 years PFSs were 20.1% and 16.1%. Myelosuppression was the most common toxicity. In 15 (19.2%) patients grade 2-3 lung toxicity and in seven (8.5%) patients' grade 2-3 dysphagia were reported. Concurrent CRT with cisplatin and etoposide schedule is a well-tolerated regimen with acceptable toxicity profile and survival rates in patients with unresectable Stage IIIA/IIIB NSCLC. Median survival and OS results were consistent with the literature.

Diagnostic value of cyclin-dependent kinase/cyclin-dependent kinase inhibitor expression ratios as biomarkers of locoregional and hematogenous dissemination risks in oral squamous cell carcinoma.

The aim of the present study was to investigate the diagnostic value of cell cycle-related genes in oral squamous cell carcinoma (OSCC) by examining the expression of the following genes in 77 OSCC tissues by quantitative polymerase chain reaction: Cyclin genes (CCNA1, CCND1, CCND2 and CCNE1), cyclin-dependent kinase (CDK) genes (CDK1, CDK2 and CDK4), CDK inhibitor genes (CDKN2A, CDKN1A, CDKN1B and CDKN1C), and integrin and associated genes that we previously reported (ITGA3, ITGB4, CD9 and JUP). The expression ratios of 66 combinations of the 11 cell cycle-related genes were analyzed to examine their associations with major clinical events using Mann-Whitney U and log-rank tests. Three expression ratios (CDK1/CDKN1B, CDK2/CDKN1A and CCNE1/CDK2) showed associations on univariate analyses and their diagnostic value was re-analyzed with integrin gene expression biomarkers (ITGA3/CD9 and ITGB4/JUP) using the Cox proportional hazards model and Kaplan-Meier estimates. Lymph node metastasis occurred in >90% of double-positive cases (high-ITGA3/CD9 and high-CDK1/CDKN1B) irrespective of tumor size (P<0.0001). Primary site recurrence was found in >30% of double-positive cases (high-ITGA3/CD9 and high-CDK2/CDKN1A) with tumors >20 mm (P=0.003). Triple-positive (high-ITGB4/JUP, high-ITGA3/CD9 and high-CDK2/CDKN1A) was associated with distant metastasis (P<0.0001), but not with other clinical parameters. Disease-specific death occurred in 55% of double-positive cases (high-ITGA3/CD9 and high-CDK2/CDKN1A) (P<0.0001) and a positive surgical margin was a significant factor for fatality in these cases. Reliable prediction of locoregional and hematogenous dissemination risks in OSCC using the four CDK and integrin gene expression ratios is a promising biomarker system. Clinical use of these parameters may improve the control rate with the use of new therapeutic strategies.

PTU-213 Oncological outcomes following local excision with and without (chemo)-radiotherapy for anal margin squamous cell carcinoma

Introduction The mainstay of treatment for anal squamous cell carcinoma (ASCC) is chemo-radiotherapy (CRT). Less than 5% of initial presentations are confined to the anal margin and amenable to local excision (LE) with or without post-operative (C)RT. However, treatment is poorly defined and outcome is understudied. Method PLATO is the next UK anal cancer trial; a three-part umbrella trial where the first stream (ACT 3) is a phase II study to assess the use of LE, for T1N0 anal margin tumours, combined with low-dose post-operative CRT (41.4Gy in 23 fractions) for close margins (≤ 1 mm), evaluated against a minimally tolerated loco-regional actuarial relapse rate of 10%. To inform this trial, we report the characteristics, treatment and outcomes of patients treated through a large anal cancer MDT (2004 to 2013), supplemented by a literature review. Results From 446 patients with new ASSC, there were 20 (4%) anal margin tumours treated by LE. Thirteen (65%) were T1; 7 (35%) were T2. All were N0 and M0. The lateral and deep margins were close (≤ 1 mm) in seven patients (35%). Five patients had additional therapy: 2 RT; 3 CRT. With a median follow-up of 38.6 months, there were no primary site recurrences; 3 patients developed nodal relapses (3-year loco-regional relapse = 11%). Three patients died attributed to their disease – the 3-year disease-free survival rate was 89%. The literature search identified six studies – there was a near total paucity of data on tumour characteristics, excision margin status, and the impact of these on subsequent treatment or outcome. Conclusion There is a need for a contemporaneous prospective study of this sub-population of patients with anal cancer, through centralisation of patients to anal cancer MDTs with pro-active identification and recruitment of these patients for the ACT3 trial. Disclosure of interest None Declared.

Outcome of Laser Surgery and Radiotherapy in Early Laryngeal Cancer

The study was undertaken to compare between surgery and radiotherapy in early carcinoma larynx (T1N0). 60 cases of early carcinoma larynx were selected purposive sampling technique from all the patients of carcinoma larynx admitted into Otolaryngology and Head-Neck Surgery Department of Bangabandhu Sheikh Mujib Medical University,Dhaka; Dhaka Medical College Hospital,Dhaka; Shaheed Suhrawardy Medical College Hospital, Dhaka; Taqwah Specialized Hospital,Dhaka from January 2010 to June 2011. Carcinoma of the larynx is the most common cancer affecting the head and neck region. The main aim of this study was to determine whether there was any difference in the two main therapeutic options. The secondary aim was to assess speech and voice quality in a small, randomized sample of patients from each treatment group. The subjects investigated were 60 patients with T1N0 squamous cell carcinoma of the larynx. 30 patients were treated by irradiation, and 30 were treated with surgery. The primary outcome measures were recurrence at the primary site, recurrence in the neck. The secondary outcome measure was speech and voice quality. Surgery included laser assisted partial laryngectomy and various minor procedures on the glottis, including cordectomy. Surgery was more likely to be carried out for supraglottic disease. Result showed 16.67% of the irradiation group had a primary site recurrence compared with 20.0% in the surgery group at 12th months (p = 0.59) and 6.67% of those who were treated with irradiation had a recurrence in the neck. 16.67% of patients in the surgery group had a recurrence in the neck (p &lt; 0.05). There was no significant difference in primary site recurrence rates for the two treatment modalities, but regional recurrence was higher in the surgery group. Regarding speech and voice quality, radiotherapy was far superior to surgery. All patients in the radiotherapy group but only 3 of 10 in the surgery group were judged to have a good or normal voice (p = .0017). Both surgery and irradiation are equally effective at treating early laryngeal carcinoma but Speech and voice quality were significantly better in patients treated by irradiation than those treated by surgery. DOI: http://dx.doi.org/10.3329/medtoday.v26i1.21312 Medicine Today 2014 Vol.26(1): 41-45

FDG volumetric parameters and survival outcomes after definitive chemoradiotherapy in patients with recurrent head and neck squamous cell carcinoma.

The purpose of this study was to establish the predictive value of (18)F-FDG parameters for overall survival in biopsy-proven recurrent head and neck squamous cell cancer (HNSCC) patients after definitive chemoradiotherapy. We conducted a retrospective study including 34 patients with HNSCC who had biopsy-proven recurrence between April 2004 and March 2012 and underwent FDG PET/CT at our institution at the time of recurrence. Maximum standardized uptake value (SUVmax), peak SUV (SUVpeak), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured. The primary outcome measure was overall survival. ROC analysis, univariate and multivariate Cox regression models, and Kaplan-Meir survival curves were performed. In univariate analyses, human papillomavirus (HPV) status (p = 0.04), primary site recurrence of MTV (p = 0.03), metastasis of MTV (p = 0.02), metastasis of TLG (p = 0.02), total MTV (p = 0.002), and total TLG (p = 0.04) were significantly associated with overall survival outcome. Total MTV remained as significant independent prognostic factor when adjusted for all other covariates except for primary site recurrence SUVmax and SUVpeak and lymph node SUVmax and SUVpeak. There was a significant difference in time to survival between patients with total MTV above and below the 50th percentile (Mantel-Cox log-rank test, p = 0.05 and Gehan-Breslow-Wilcoxon test, p = 0.03) and the optimum threshold of 16.8 mL (Mantel-Cox log-rank test, p = 0.01 and Gehan-Breslow-Wilcoxon test, p = 0.01; hazard ratio [HR], 0.25). FDG PET/CT-based total MTV and clinical HPV status may be significant prognostic markers for overall survival of patients with recurrent HNSCC after definitive chemoradiotherapy.

Extraneural Metastases of Glioblastoma without Simultaneous Central Nervous System Recurrence.

Glioblastoma multiforme (GBM) is well known as the most common malignant primary brain tumor. It could easily spread into the adjacent or distant brain tissue by infiltration, direct extension and cerebro-spinal fluid dissemination. The extranueural metastatic spread of GBM is relatively rare but it could have more progressive disease course. We report a 39-year-old man who had multiple bone metastases and malignant pleural effusion of the GBM without primary site recurrence.

Local treatment of oligometastatic recurrence in patients with resected non-small cell lung cancer

ObjectivesWe previously reported a retrospective study indicating the prognostic impact of the local treatment of oligometastatic recurrence after a complete resection for non-small cell lung cancer (NSCLC). In the present study, we prospectively observed postoperative oligometastatic patients and investigated the effects of local treatment on progression-free survival (PFS). MethodsUsing a prospectively maintained database of patients with completely resected NSCLC treated between October 2007 and December 2011, we identified 52 consecutive patients with postoperative recurrence, excluding second primary lung cancer. Of these patients, 31 suffering from distant metastases alone without primary site recurrence were included in this study. According to the definition of ‘oligometastases’ as a limited number of distant metastases ranging from one to three, 17 patients had oligometastatic disease. Of those 17 patients, four patients with only brain metastasis were excluded from the analysis. ResultsThe oligometastatic sites included the lungs in five patients, bone in four patients, the lungs and brain in two patients, the adrenal glands in one patient and soft tissue in one patient. Eleven of the 13 patients first received local treatment. Three patients (lung, adrenal gland, soft tissue) underwent surgical resection, and the remaining eight patients received radiotherapy. The median PFS was 20 months in the oligometastatic patients who received local treatment. There were five patients with a PFS of longer than two years. The metastatic sites in these patients varied, and one patient had three lesions. On the other hand, the two remaining patients first received a systemic chemotherapy of their own selection. The PFS of these two patients was five and 15 months, respectively. ConclusionLocal therapy is a choice for first-line treatment in patients with postoperative oligometastatic recurrence.

ITGA3 and ITGB4 expression biomarkers estimate the risks of locoregional and hematogenous dissemination of oral squamous cell carcinoma

BackgroundMolecular biomarkers are essential for monitoring treatment effects, predicting prognosis, and improving survival rate in oral squamous cell carcinoma. This study sought to verify the effectiveness of two integrin gene expression ratios as biomarkers.MethodsGene expression analyses of integrin α3 (ITGA3), integrin β4 (ITGB4), CD9 antigen (CD9), and plakoglobin (JUP) by quantitative real-time PCR were conducted on total RNA from 270 OSCC cases. The logrank test, Cox proportional hazards model, and Kaplan-Meier estimates were performed on the gene expression ratios of ITGA3/CD9 and ITGB4/JUP and on the clinicopathological parameters for major clinical events.ResultsA high rate (around 80%) of lymph node metastasis was found in cases with a high ITGA3/CD9 ratio (high-ITGA3/CD9) and invasive histopathology (YK4). Primary site recurrence (PSR) was associated with high-ITGA3/CD9, T3-4 (TNM class), and positive margin, indicating that PSR is synergistically influenced by treatment failure and biological malignancy. A high ITGB4/JUP ratio (high-ITGB4/JUP) was revealed to be a primary contributor to distant metastasis without the involvement of clinicopathological factors, suggesting intervention of a critical step dependent on the function of the integrin β4 subunit. Kaplan-Meier curves revealed positive margin as a lethal treatment consequence in high-ITGA3/CD9 and YK4 double-positive cases.ConclusionTwo types of metastatic trait were found in OSCC: locoregional dissemination, which was reflected by high-ITGA3/CD9, and distant metastasis through hematogenous dissemination, uniquely distinguished by high-ITGB4/JUP. The clinical significance of the integrin biomarkers implies that biological mechanisms such as cancer cell motility and anchorage-independent survival are vital for OSCC recurrence and metastasis.

Elective Neck Dissection for N0 Neck During Salvage Total Laryngectomy

Optimum management of the clinically negative neck in the presence of primary site recurrence of laryngeal or hypopharyngeal cancer remains unclear. To examine the incidence of occult cervical nodal metastatic disease in patients undergoing salvage laryngectomy with necks clinically staged as N0 at the time of recurrence and to define the role of elective neck dissection in this population with regard to risk of complications and oncologic outcomes. Retrospective study of patients treated from 1996 through 2011. Academic teaching hospital. All patients undergoing salvage total laryngectomy for squamous cell carcinoma of larynx or hypopharynx after failed initial radiotherapy or chemoradiotherapy with radiographically N0 neck at time of recurrence. Primary outcome measure was incidence of cervical nodal metastases detected by means of pathological examination of elective neck dissection specimens. Secondary outcome measures were incidence of major postoperative complications and regional cancer control. Forty-five patients were included. Thirty-eight underwent elective unilateral (20) or bilateral (18) ND at the time of laryngectomy. Three patients (8%) had occult metastases (3 of 56 dissected heminecks [5%]). The incidence of major wound complications was significantly greater in patients undergoing bilateral ND (12 of 18 [67%]) than in patients undergoing unilateral or no ND (8 of 27 [30%]) (P = .03). There was no significant difference in regional control according to whether bilateral, unilateral, or no ND was performed. The incidence of occult metastatic disease in N0 necks in patients undergoing salvage surgery after radiotherapy is low. Neck dissection in this population does not seem to have a significant impact on regional cancer control. The need for elective ND, particularly bilateral ND, should be balanced against possible increased risk of morbidity in this group.

Melanoma Patients with Unknown Primary Site or Nodal Recurrence after Initial Diagnosis Have a Favourable Survival Compared to Those with Synchronous Lymph Node Metastasis and Primary Tumour

BackgroundA direct comparison of prognosis between patients with regional lymph node metastases (LNM) detected synchronously with the primary melanoma (primary LNM), patients who developed their first LNM subsequently (secondary LNM) and those with initial LNM in melanoma with unknown primary site (MUP) is missing thus far.Patients and MethodsSurvival of 498 patients was calculated from the time point of the first macroscopic LNM using Kaplan Meier and multivariate Cox hazard regression analysis.ResultsPatients with secondary LNM (HR = 0.67; p = 0.009) and those with initial LNM in MUP (HR = 0.45; p = 0.008) had a better prognosis compared to patients with primary LNM (median survival time 52 and 65 vs. 24 months, respectively). A high number of involved nodes, the presence of in-transit/satellite metastases and male gender had an additional independent unfavourable effect.ConclusionsSurvival of patients with LNM in MUP and with secondary LNM is similar and considerably more favourable compared to those with primary LNM. This difference needs to be considered during patient counselling and for stratification purposes in clinical trials. The assumption of an immune privilege of patients with MUP which is responsible for rejection of the primary melanoma, and results in a favourable prognosis is not supported by our data.

Patterns of Disease Recurrence Following Treatment of Oropharyngeal Cancer With Intensity Modulated Radiation Therapy

To report mature results of a large cohort of patients diagnosed with squamous cell carcinoma of the oropharynx who were treated with intensity modulated radiation therapy (IMRT). The database of patients irradiated at The University of Texas, M.D. Anderson Cancer Center was searched for patients diagnosed with oropharyngeal cancer and treated with IMRT between 2000 and 2007. A retrospective review of outcome data was performed. The cohort consisted of 776 patients. One hundred fifty-nine patients (21%) were current smokers, 279 (36%) former smokers, and 337 (43%) never smokers. T and N categories and American Joint Committee on Cancer group stages were distributed as follows: T1/x, 288 (37%); T2, 288 (37%); T3, 113 (15%); T4, 87 (11%); N0, 88(12%); N1/x, 140 (18%); N2a, 101 (13%); N2b, 269 (35%); N2c, 122 (16%); and N3, 56 (7%); stage I, 18(2%); stage II, 40(5%); stage III, 150(19%); and stage IV, 568(74%). Seventy-one patients (10%) presented with nodes in level IV. Median follow-up was 54 months. The 5-year overall survival, locoregional control, and overall recurrence-free survival rates were 84%, 90%, and 82%, respectively. Primary site recurrence developed in 7% of patients, and neck recurrence with primary site control in 3%. We could only identify 12 patients (2%) who had locoregional recurrence outside the high-dose target volumes. Poorer survival rates were observed in current smokers, patients with larger primary (T) tumors and lower neck disease. Patients with oropharyngeal cancer treated with IMRT have excellent disease control. Locoregional recurrence was uncommon, and most often occurred in the high dose volumes. Parotid sparing was accomplished in nearly all patients without compromising tumor coverage.