Recurrent Primary Tumors Research Articles

Is elective neck dissection indicated during salvage surgery for head and neck squamous cell carcinoma?

Among patients with head and neck squamous cell carcinoma with a negative neck who are initially treated with (chemo)radiotherapy, a number of cases will recur locally without obvious neck recurrence. There is little information available as to the most efficacious management of the neck in these cases. We have reviewed the literature to see what conclusions can be drawn from previous reports. We conducted a bibliography search on MEDLINE and EMBASE databases. Studies published in the English language and those on squamous cell carcinoma of the oral cavity, nasopharynx, oropharynx, larynx and hypopharynx were included. Data related to neck management were extracted from the articles. Twelve studies satisfied the inclusion criteria. Five studies reported only one treatment plan (either neck dissection or observation), while the others compared neck dissection to observation. The rate of occult metastases ranged from 3.4 to 12 %. The studies included a variable distribution of primary sites and stages of the recurrent primary tumors. The risk of occult neck node metastasis in a clinically rN0 patient correlated with tumor site and T stage. Observation of the neck can be suggested for patients with T1-2 glottic tumors, who recurred with less advanced tumors (rT1-2). For patients with more advanced laryngeal recurrences or recurrence at other high-risk sites, neck dissection could be considered for the rN0 patient, particularly if the neck was not included in the previous radiation fields.

Oral cancer and oral potentially malignant disorders.

Oral cancer and oral potentially malignant disorders.

High‐dose chemotherapy followed by autologous peripheral blood stem cell transplantation for recurrent primary mediastinal malignant germ cell tumor: A case report

A 15-yr-old boy presented with an anterior mediastinal mass, multiple lung metastases and obstruction of the left brachiocephalic vein, the superior vena cava and the subclavian vein. Tumor biopsy by CT guidance confirmed a diagnosis of GCT. Five courses of BEP therapy were performed, and CT of the chest revealed reduction in the anterior mediastinal mass and disappearance of the multiple lung metastases. We performed the anterior mediastinal mass extraction followed by adjuvant chemotherapy consisting of ICE and TIP. However, the AFP levels became elevated soon after. Abnormal accumulation was observed in the right upper lung by DW-MRI. After the operation, two courses of TI chemotherapy and two courses of HDCT followed by auto-PBSCT were performed. He was complicated with auditory disorder and renal dysfunction. Although HDCT followed by auto-PBSCT was effective for the relapsed primary mediastinal GCT, a treatment strategy avoiding late complications is warranted.

CTNNB1 45F mutation is a molecular prognosticator of increased postoperative primary desmoid tumor recurrence

A role for the serine to phenylalanine substitution at codon 45 (the S45F mutation) in the catenin (cadherin-associated protein) β-1 (CTNNB1) gene as a molecular predictor of local recurrence in patients with primary, sporadic desmoid tumor (DT) has been reported. To confirm the previous data, the authors evaluated the correlation between CTNNB1 mutation type and local recurrence in this multi-institutional, retrospective study. Patients with primary, sporadic DT who underwent macroscopic complete surgical resection were included. Recurrence-free survival (RFS) analyses were conducted using the Kaplan-Meier method and log-rank tests to compare strata. In total, 179 patients were identified, including 65% females and 35% males (median age, 39 years; median tumor size, 7 cm). Most DTs were located in the abdominal/chest wall (42%) followed by extra-abdominal sites (40%) and intra-abdominal sites (18%). All patients underwent either R0 resection (62%) or R1 resection (38%), and most underwent surgery alone (80%). The tyrosine to alanine substitution at codon 41 (T41A) was the most frequent mutation (45%), but the S45F mutation was more prevalent in extra-abdominal DTs compared with other sites (P< .001). At a median follow-up of 50 months, 86% of patients remained alive without disease. The estimated 3-year and 5-year RFS rates were 0.49 and 0.45, respectively, for patients who had tumors with the S45F mutation; 0.91 and 0.91, respectively, for patients who had wild-type tumors; and 0.70 and 0.66, respectively, for all others (P< .001). A similar trend was observed for patients who underwent surgery alone (P< .001). On multivariable analysis, mutation remained the only factor that was prognostic for local recurrence. This series confirmed that primary, completely resected, sporadic DTs with the S45F mutation have a greater tendency for local recurrence. With increasing implementation of "watchful-waiting" for DT management, it will be important to determine whether mutation type predicts outcome for these patients.

Elimination of Metastatic Melanoma Using Gold Nanoshell-Enabled Photothermal Therapy and Adoptive T Cell Transfer

Ablative treatments such as photothermal therapy (PTT) are attractive anticancer strategies because they debulk accessible tumor sites while simultaneously priming antitumor immune responses. However, the immune response following thermal ablation is often insufficient to treat metastatic disease. Here we demonstrate that PTT induces the expression of proinflammatory cytokines and chemokines and promotes the maturation of dendritic cells within tumor-draining lymph nodes, thereby priming antitumor T cell responses. Unexpectedly, however, these immunomodulatory effects were not beneficial to overall antitumor immunity. We found that PTT promoted the infiltration of secondary tumor sites by CD11b+Ly-6G/C+ myeloid-derived suppressor cells, consequently failing to slow the growth of poorly immunogenic B16-F10 tumors and enhancing the growth of distant lung metastases. To exploit the beneficial effects of PTT activity against local tumors and on antitumor immunity whilst avoiding the adverse consequences, we adoptively transferred gp100-specific pmel T cells following PTT. The combination of local control by PTT and systemic antitumor immune reactivity provided by adoptively transferred T cells prevented primary tumor recurrence post-ablation, inhibited tumor growth at distant sites, and abrogated the outgrowth of lung metastases. Hence, the combination of PTT and systemic immunotherapy prevented the adverse effects of PTT on metastatic tumor growth and optimized overall tumor control.

Late tumor pseudoprogression followed by complete remission after lung stereotactic ablative radiotherapy

Lung stereotactic ablative radiotherapy (SABR) has recently become more common in the management of patients with early-stage non-small cell lung cancer (NSCLC) and metastatic lung lesions who are not surgical candidates. By design, SABR is applied to small treatment volumes, using fewer but significantly higher dose fractions, and steep dose gradients. This treatment theoretically maximizes tumor cell death and decreases the risk of damage to the surrounding normal tissues. Local control rates for SABR in early stage lung cancer remain high. Since the numbers of primary tumor recurrences is small, some debate exists as to the appropriate definition of treatment failure. Controversies remain regarding the most appropriate interpretation of imaging tests obtained to evaluate treatment outcomes after lung SABR. Most definitions of progression include an increasing diameter of target lesion which can be problematic given the known mass-like consolidation seen on CT imaging after ablative therapy. Here, we present a case report illustrative of the pitfalls of relying solely on anatomic imaging to determine SABR treatment failure.

Wilms Tumor

Wilms Tumor

Bioluminescent Orthotopic Model of Pancreatic Cancer Progression

Pancreatic cancer has an extremely poor five-year survival rate of 4-6%. New therapeutic options are critically needed and depend on improved understanding of pancreatic cancer biology. To better understand the interaction of cancer cells with the pancreatic microenvironment, we demonstrate an orthotopic model of pancreatic cancer that permits non-invasive monitoring of cancer progression. Luciferase-tagged pancreatic cancer cells are resuspended in Matrigel and delivered into the pancreatic tail during laparotomy. Matrigel solidifies at body temperature to prevent leakage of cancer cells during injection. Primary tumor growth and metastasis to distant organs are monitored following injection of the luciferase substrate luciferin, using in vivo imaging of bioluminescence emission from the cancer cells. In vivo imaging also may be used to track primary tumor recurrence after resection. This orthotopic model is suited to both syngeneic and xenograft models and may be used in pre-clinical trials to investigate the impact of novel anti-cancer therapeutics on the growth of the primary pancreatic tumor and metastasis.

Changes in the biologic markers between primary tumor and ipsilateral breast tumor recurrence after breast conserving surgery: Discordance and prognosis.

1116 Background: Changes in biological markers due to recurrence are clinically experienced in breast cancer. However, the clinical significance is still uncertain, especially after breast conserving surgery. The changes in biological markers between primary tumor and ipsilateral breast tumor recurrence (IBTR) and their correlations with prognosis were investigated, retrospectively. Methods: A total of 117 consecutive patients with IBTR without distant metastases were enrolled in this study. All patients were examined for ER, PgR, HER2 and Ki-67 in both the primary and recurrent tumors. The cases were categorized into 3 groups: patients with Ki-67 values &lt;20%, &lt;50% and ≥50%, and divided into 2 groups according to the IBTR site, same quadrant(SQ)and different quadrant(DQ) from the initial sites. The distant disease-free survival (DDFS) was calculated using the Kaplan-Meier method and evaluated by the log-rank test and multivariate analyses using Cox proportional hazards model. The median follow-up period was 4.8 years after IBTR. Results: The PgR positive rate from the primary tumor to IBTR decreased from 57% to 39% and the Ki-67 values increased significantly from a mean of 17% to 23%. The concordance rate of the subtype was 62%. In the SQ group, the PgR positive rate significantly decreased and the mean Ki-67 values significantly increased, whereas there was no significant difference in the DQ group. In terms of changes by category due to relapse, the discordance rate in Ki-67 was high in the SQ group, and HER2 was high in the DQ group. Regarding DDFS by a change in the categorization, the cases with discordance in Ki-67 values had significantly lower DDFS in the SQ group(5-year DDFS: 75% vs 52%, p=0.04). However, a clear difference was not found in the DQ group. Conclusions: The PgR positive rate decreased while the mean Ki-67 values increased due to IBTR in the SQ group. The categorical discordance in the Ki-67 values was significantly associated with lower DDFS, especially in the SQ group. These findings suggest that the recurrent site and change in the biological markers were clinical significant in the evaluation of the characteristics and treatment in cases with IBTR.

PP149: Experience of the lip cancer treatment in latvian oncological center: 10 year review

Purpose A review of 201 patients who were diagnosed with lip cancer from 2001 to was undertaken to analyse the epidemiological data, to compare the results of surgical and radiation therapy and evaluate long term follow-up. Material and methods From 2001 to 2011, 201 patients (151 males and 50 females) with a primary squamous cell carcinoma of the lower lip were treated. Median age of patients was 65,4 years. 88 patients (43.7%) had I stage disease, 68 patients (33.9%) – II stage, 30 patients – III stage and 15 patients (7.5%) IV stage disease. At presentation, regional lymph nodes were clinically negative in 181 patients.100 patients underwent surgical excision as a primary treatment. Vermilionectomy was performed to five patients. “V” excision were performed to 63 patients, Reconstruction by Abbe flap was performed to 22 patients. Estlander method to four patients. According to J. Liu modified labila tissue sliding flaps for repairing lower lip defects were used in three cases, “stair case technique” were used in three cases. The cases classified as T3 (defects of 65–80%) were reconstructed with cheek advancement flaps in different types (Webster Bernard approach, Karapandzic technique, “Fan flap”) and nasolabial flap also. Microsurgical repair was used in five cases of total lip defect. 56 patients had radiotherapy as the primary mode of therapy and 45 patients received combined method of treatment (surgery and irradiation). In the patients group with clinically negative neck at the first attendance (181 patients), in the follow-up delayed cervical lymph node metastases developed in 12 patients (6.6%) within 2 years of follow-up. 32 patients underwent different types of neck dissections. Results The results of surgery were generally good Recurrence of primary tumor developed in 28 patients (13.9%) and was strongly associated with large tumor size, comissure tumors and poor differentiation. The determinate mean survival rate was found to be 82.4% at 2 yar follow-up. Conclusions We recommend surgery as the primary method of treatment because of the availability of histologically accurate tumour margin assessment and the short rehabilitation period.

Metachronous Occurrence of Triple Malignancies of Kidneys, Prostate, and Breast. A Case Report and Review of The Literature

Multiple consecutive cancers involving different organs in a male individual are presented. Case Presentation. Herein, we present a rare case of primary right renal cell carcinoma (RCC), in which two different organ malignancies of prostate and breast were occurred consecutively. After proper treatment of each organ tumor, the patient experienced metachronous occurrence of its final tumor in his remained left kidney as left side RCC. Discussions. Multiple primary cancers are defined as occurrence of two or more malignancies, synchronous or metachronous, in different organs without any relation to each other. For primary and secondary tumors of the male genitourinary system, the most common occurrence was tumors of bladder and prostate followed by tumors of the kidney. Our case was a rare presentation of consecutive occurrence of multiple organ tumors: right side RCC, adenocarcinoma of prostate, and ductal cell carcinoma of the left breast, followed by left side RCC. Conclusions. In any case of primary malignancy of any organ, not only primary tumor recurrence but also tumoral growth of other nonrelated organs should be evaluated, especially in high risk patients or patients with positive familial history.

Dielectrophoresis has broad applicability to marker-free isolation of tumor cells from blood by microfluidic systems

The number of circulating tumor cells (CTCs) found in blood is known to be a prognostic marker for recurrence of primary tumors, however, most current methods for isolating CTCs rely on cell surface markers that are not universally expressed by CTCs. Dielectrophoresis (DEP) can discriminate and manipulate cancer cells in microfluidic systems and has been proposed as a molecular marker-independent approach for isolating CTCs from blood. To investigate the potential applicability of DEP to different cancer types, the dielectric and density properties of the NCI-60 panel of tumor cell types have been measured by dielectrophoretic field-flow fractionation (DEP-FFF) and compared with like properties of the subpopulations of normal peripheral blood cells. We show that all of the NCI-60 cell types, regardless of tissue of origin, exhibit dielectric properties that facilitate their isolation from blood by DEP. Cell types derived from solid tumors that grew in adherent cultures exhibited dielectric properties that were strikingly different from those of peripheral blood cell subpopulations while leukemia-derived lines that grew in non-adherent cultures exhibited dielectric properties that were closer to those of peripheral blood cell types. Our results suggest that DEP methods have wide applicability for the surface-marker independent isolation of viable CTCs from blood as well as for the concentration of leukemia cells from blood.

Extranodal B Cell Lymphoma Spreading from Skin to Oral Cavity

ABSTRACT Non-Hodgkin's lymphoma (NHL) belongs to a group of lymphoid neoplasms that is diverse in manner of presentation, response to therapy and prognosis. Usually oral manifestations of NHL are secondary to a more widespread involvement throughout th e bo dy. Tho ugh primary in traoral lesio ns in NHL are uncommon, it is important to be aware of them, since intraoral manifestations are the presenting symptoms in these patients.2 A 58-year-old man presented to our Department with swelling in the vestibule of mouth. CT scan revealed a mass on upper gingival without any bony involvement. Incisional biopsy of the lesion showed diffuse large B cell lymphoma. The patient was treated successfully with chemotherapy. One year after complete remission, patient developed recurrence of primary tumor for which patient was again given chemotherapy treatment but had no significant benefit and succumb to the disease. How to cite this article Kaul A, Kalsotra P. Extranodal B Cell Lymphoma Spreading from Skin to Oral Cavity. Int J Head Neck Surg 2013;4(3):126-128.

Concurrent Chemo-Proton Therapy Using 5-fluorouracil and Cisplatin for Esophageal Cancer

Concurrent Chemo-Proton Therapy Using 5-fluorouracil and Cisplatin for Esophageal Cancer

Pre-Chemoradiation Therapy FDG PET/CT Cannot Identify Residual Metabolically Active Areas in Patients With Locally Advanced Esophageal Cancer

completion of the combined therapy, upper gastrointestinal endoscopy and computed tomography scans were performed for follow-up examination at 2-6 months intervals. Results: All patients successfully completed proton beam therapy. Of the 14 patients, 11 (79%) showed a complete response, and 3 (21%) showed a partial response. Distant metastasis was observed in 4 (29%) patients. Two patients had in-field recurrences: both of primary tumor recurrences and mediastinal lymph node metastases were observed 9 and 16 months after the completion of proton beam therapy. With a median follow-up of 15 months (range, 9-37 months), the rate of local tumor control, and the actuarial overall survival at 1 year were 90% and 93%, respectively. Regarding acute treatment-related toxicity, grade 3 or higher esophagitis and hematological toxicities were noted in 5 (36%) and 3 (21%) patients, respectively. Grade 2 severe late neither pulmonary nor cardiac toxicities was observed in the present study. Conclusions: Concurrent chemo-proton therapy using 5-fluorouracil and cisplatin would be an effective alternative radiation therapy as non-surgical but curative treatment option for esophageal cancer with minimizing toxicities of the lung or the heart. Author Disclosure: T. Hashimoto: None. H. Ishikawa: None. T. Okumura: None. H. Makishima: None. T. Ohno: None. A. Kanemoto: None. H. Hashii: None. A. Ohkawa: None. M. Mizumoto: None. H. Sakurai: None.

Radiofrequency ablation of non-resectable lung tumors

Radiofrequency thermal ablation (RFA) is a minimally invasive, image guided technique for destroying tumour cells without damage to adjacent healthy tissue. It is used for partial or complete ablation of non resectable lung cancers and cancers of metastases to lung, providing an effective, relatively safe option for patients ineligible for surgery. We describe our experience with it. In 2005 and 2006, we performed radiofrequency ablation of 7 lung lesions in 6 patients. RFA was done percutaneously under image guided CT scan in 5 patients and in one patient during thoracotomy when we found a radically unresectable tumor necessitating debulking. CT lung screening was performed after 6 months and PET/CT was done within 12 months. In the course of the screening, we diagnosed regression in 2 patients, a stationary state in 2 cases and local tumor progression in 2 patients, using computed tomography within 6 months after RFA. Using PET/CT within 12 months, we diagnosed non-ablation and liver metastases (there were none before) in one of the two patients with a stationary state diagnosed by means of CT before and recurrence of primary tumor in another patient. In one case of diagnosed regression, we diagnosed tumor progression. The patients survived an average of 30 months (range 9 to 60 months). RFA of lung tumors is an easy method with little patient discomfort. It can be performed percutaneously using guided CT under general anaesthesia. RFA of lung tumors possibly alone or in combination with oncology treatment can prolong patient life.

Intraoperative 32P High-Dose Rate Brachytherapy of the Dura for Recurrent Primary and Metastatic Intracranial and Spinal Tumors

Treatment of spinal and intracranial tumors with dural involvement is complicated by radiation tolerance of sensitive structures, especially in the setting of previous treatment. To evaluate whether intraoperative brachytherapy with short-range sources allows therapeutic dose delivery without damaging sensitive structures. The median doses of previous treatment were 3000 cGy (range, 1800-7200 cGy) for 8 patients with primary/recurrent and 17 patients with metastatic spinal tumors and 5040 cGy (range, 1300-6040 cGy) for 5 patients with locally recurrent and 2 patients with metastatic intracranial tumors. Patients underwent gross total or maximal resection of the tumor and were then treated with an intraoperative brachytherapy plaque consisting of a flexible silicone film incorporating P. A dose of 1000 cGy was delivered to a depth of 1 mm; the percent depth dose was less than 1% at 4 mm from the prescription depth. Median postoperative radiation doses of 2700 cGy (range, 1800-3000 cGy) were delivered to 15 spinal tumor patients and 3000 cGy (range, 1800-3000 cGy) to 3 intracranial tumor patients. The median follow-up was 4.4 months (range, 2.6-23.3 months) for spinal tumor patients and 5.3 months (range, 0.7-16.2) for intracranial tumor patients. At 6-month follow-up, for all spinal tumor patients, local progression-free survival and overall survival rates were both 83.3% (95% confidence interval [CI]: 62.3%-94.3%); for all intracranial tumor patients, the local progression-free survival rate was 62.5% (95% CI: 23.8%-90.9%) and the overall survival rate was 66.7% (95% CI: 26.7%-92.9%). There were no intraoperative or postoperative complications secondary to radiotherapy. Use of the P brachytherapy plaque is technically simple and not associated with increased risk of complications, even after multiple radiation courses. Local control rates were more than 80% in patients with proven radiation-resistant spinal disease.

Regional control after concomitant chemoradiotherapy without planned neck dissection in node-positive head and neck squamous cell carcinomas

Although three-weekly high-dose (100mg/m(2)) cisplatin (three cycles) chemoradiotherapy has been considered a standard regimen for patients with advanced head and neck squamous cell carcinomas (HNSCC), this protocol is associated with significant acute and late toxicities. Therefore, weekly cisplatin at a dose of 40mg/m(2) has been used at our institution since 2006. This retrospective study was aimed at assessing the oncologic efficacy of weekly cisplatin chemoradiotherapy for the control of nodal metastasis. We analyzed 28 patients with node-positive HNSCC treated with weekly cisplatin and concurrent radiotherapy. Computed tomography was performed 4-8 weeks after the completion of chemoradiotherapy to evaluate nodal response. If residual neck disease was apparent or suspected, we performed early salvage neck dissection (ND). In cases with a complete response (CR), we took a "wait and see" approach. When no viable tumor cells were observed in the surgical specimens obtained by ND, nodal metastasis was defined as controlled by weekly cisplatin chemoradiotherapy alone. Nodal metastasis was evaluated as having a CR in 20 patients (71%). Eight patients (29%) underwent early salvage ND. Recurrent primary tumors were observed in the other four patients (14%). Salvage primary resection and associated ND were performed for these four patients. In 7 of 12 patients undergoing ND, no viable tumor cells were observed. In 23of 28 patients, neck diseases were controlled by chemoradiotherapy alone (not including salvage by ND). In 27 of 28 patients, neck diseases were controlled by the overall treatment (including salvage by ND). The rate of nodal control by chemoradiotherapy alone and by the overall treatment was found to be 82.0% and 96.3%, respectively, using the Kaplan-Meier method. The three-year overall and disease free survival rates were 86.8% and 80.8%, respectively. Concomitant weekly cisplatin at a dose of 40mg/m(2) chemoradiotherapy showed a good control rate of not only primary lesions but also neck diseases.

Late skip lymph node metastasis of oral squamous cell carcinoma or metastasis of unknown second primary tumor? Answer by mitochondrial DNA analysis

Patients with head and neck squamous cell carcinoma (SCC) are at risk of developing additional tumors in the head and neck. The detection of a late lymph node metastasis poses a problem to the clinician: it could be a delayed regional metastasis or a new metastasis from a yet unknown second primary tumor. Differentiation between metastasis and recurrence of primary tumors versus second primary tumor may be difficult because all lesions have the histologic appearance of SCC. Differentiation between these possibilities, however, carries important differences in therapeutic and prognostic consequences. In the following case report we present an unusually late regional lymph node metastasis in a patient who was treated 4 years earlier for an SCC in the inferior alveolar ridge. The purpose of the present study was to apply mitochondrial DNA D-loop analysis to assess the clonal relationship between oral tumor and node metastasis.

Correlation of pretreatment surgical staging and PET SUVmax with outcomes in NSCLC.

7051 Background: The AJCC staging does not recognize the number of involved mediastinal lymph nodes (LN), nodal stations or PET findings as prognostic factors in non-small cell lung cancer (NSCLC). Most clinical studies report poorer survival with greater number of involved LN and maximal tumor standardized uptake value (SUVmax) &gt; 5. We hypothesized that clinical outcomes can be predicted by (1) number of involved LN, (2) number of involved nodal stations, (3) SUVmax of primary tumor and (4) SUVmax of mediastinum. Methods: Records of patients diagnosed with NSCLC stages I-IIIA from 1/1/99 to 12/31/10 were reviewed. Data collected included age, type of surgery, AJCC stage, number of LN/stations sampled and SUVmax of primary tumor/mediastinum. Primary outcomes were tumor recurrence and death. Descriptive statistics were used to summarize demographics. Prognostic factors were analyzed by a multivariate analysis using Cox’s proportional hazard model. Survival was estimated by the Kaplan-Meier method. Results: There were 369 patients with complete clinical data; 207 underwent surgical staging with mediastinoscopy (62) or VATS/open thoracotomy (145). The median number of LN sampled was 9 (range 1-35) and the median number of stations biopsied was 3 (range 1-9). PET was performed in 89 patients; 59 scans showed tumor SUVmax &gt; 5. A total of 65/207 patients received chemotherapy. With median follow-up time of 29 months (range 1-116), 73 recurrences and 90 deaths were observed. Cox analysis showed greater recurrence risk for patients with 4 or more involved LN (HR= 4.66, CI=1.19-18.18, p=0.027) and higher mortality for patients with tumor SUVmax &gt; 5 (HR=14.83, CI=2.32-94.9, p=0.004). Outcomes did not correlate with the number of involved nodal stations (p=0.76 for recurrence, p=0.51 for mortality) or with SUVmax of mediastinum (p=0.17 for recurrence, p=0.93 for mortality). Conclusions: The number of involved LN was an independent prognostic factor for recurrence but not for mortality. A tumor SUVmax &gt;5 was independently associated with greater mortality. The number of involved stations and the SUVmax of mediastinum did not correlate with worse outcomes. Our results are limited due to the small number of cases with PET/CT scans and short follow-up.