Advanced Tongue Cancer Research Articles

S5. Surgical treatment for advanced tongue cancer

S5. Surgical treatment for advanced tongue cancer

Superselective intraarterial chemotherapy and concurrent radiotherapy in advanced tongue cancer

Superselective intraarterial chemotherapy and concurrent radiotherapy in advanced tongue cancer

Abstract A43: Effect of chemoradiation on oxidant-antioxidant profile and its correlation with therapeutic response in patients with carcinoma of posterior one third of tongue

Abstract Background and Objectives: Cancer of posterior one-third of tongue is seen in 0.43% of total world population. Squamous cell carcinoma of head and neck is the most common cancer encountered in India. Oxidative stress is potentially harmful to cells and ROS are involved in multistage carcinogenesis, in initiation and promotion. Moreover, the extent of ROS-induced oxidative damage can be exacerbated by decreased efficiency of antioxidant defense mechanisms. The correlation of therapeutic response on chemoradiation with the change in oxidant-antioxidant profile has not been studied till date. The aim of this study was to study the alterations in the circulating lipid peroxide, antioxidant components and the activities of defense enzymes in patients with cancer of posterior one-third of tongue and to monitor the variations in their levels before and after chemoradiation and to assess the relevance of these levels to therapeutic response. Methods: Sixty newly diagnosed patients with cancer of posterior one-third of tongue (Stage III–IVa) and 60 healthy controls were enrolled in this study. The samples were collected: before the start of therapy; after the second course of chemotherapy; two weeks after the completion of teleradiation and after 1 year on follow-up. Single blood samples were taken from controls. Lipid peroxides, conjugated dienes, reduced glutathione (GSH), catalase (CAT) and glutathione-S-transferase (GST) were estimated using standard methods. Glutathione peroxidase (GPx) and superoxide dismutase (SOD) were assayed using commercially available kits from Randox, UK. Response to therapy was assessed during and after therapy and after one year of follow-up. Results: The pre-treatment levels of plasma lipid peroxide were significantly elevated whilst significantly lowered levels of GSH, GPx, GST, SOD and CAT were observed in cancer patients, when compared to controls. After chemotherapy, the levels of lipid peroxidation showed a significant decline in complete responders, as compared with partial/non-responders; which became highly significant after completion of therapy. This fall remained significant after one year of completion of therapy during follow-up. The levels of GSH, GPx, SOD and CAT showed a mild increase (p<0.05), after chemotherapy in complete responders, as compared with partial/non-responders; which became highly significant after completion of therapy. Conclusion: This important finding suggests that pre-treatment levels of antioxidant-oxidant parameters and the extent of their change during treatment can predict the therapeutic response to chemoradiation in patients with cancer of posterior one-third of tongue A larger patient cohort with a longer follow-up period for therapeutic response studies might yield more significant data on their probable use as predictors of chemoradiosensitivity of advanced tongue cancer. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A43.

Function preservation with multimodality treatment in locally advanced oral tongue cancer

e17051 Background: Total or near total glossectomy with postoperative radiation is a standard treatment option for locally advanced squamous cell carcinoma oral tongue (LASCCOT). However, the procedure is controversial due to dismal cure rates and major functional deficits that impact on speech, deglutition and quality of life. We evaluated function preservation and survival outcome in LASCCOT treated with induction chemotherapy, limited surgery, and postoperative radiation/chemoradiation. Methods: We retrospectively identified 15 patients with LASCCOT treated with induction chemotherapy, limited surgery and postoperative radiation/chemoradiation at our institution between 04/07 - 04–08. M67%:F33% median age 50 years. Pretreatment AJCC stage as assessed on MRI was T2N+ (tumour crossing midline) 13%, T3N0 20%, T3N+ 47%, and T4N+ 20%. Prior to surgery induction chemotherapy, consisting of cisplatin 75 mg/m2 day 1 and gemcitabine 1 mg/m2 day 1 and 8 every three weeks for 2 cycles was given. Four to six weeks following second cycle of chemotherapy local excision of residual primary tumor with ipsilateral modified neck dissection was performed. Postoperative radiation dose was 60Gy/30 fractions. Post therapy pathological stage was ypT0N0 20%, ypT1N0 20%, ypT1N+ 40%, ypT2N+ 13%, and ypT3N+ 7%. Patients with ypN+ disease received concomitant 3 weekly cisplatin 75 mg/m2 with radiation. Results: Overall and disease free survival at 20 months was 60%. Twelve patients (80%) are alive and 3 patients (20%) have died of disease at 9, 14 and 14 months (locoregional failure 1 and distant metastasis 2 patients). In patients alive without disease assessment of deglutition and speech at the time of last follow up showed all patients on full oral diet with spontaneous intelligible speech. Conclusions: Multimodality treatment with induction chemotherapy, limited surgery and post operative radiation/chemoradiation may allow selected LASCCOT patients to avoid morbid surgery and preserve tongue function without compromising survival. This approach merits further investigation in clinical trials. No significant financial relationships to disclose.

Organ preservation treatment using TPF—a pilot study in patients with advanced primary and recurrent cancer of the oral cavity and the maxillary sinus

Induction chemotherapy with Taxotere, cisplatin, and 5-fluororacil (TPF) was mainly used in hypopharyngeal and laryngeal cancer patients for larynx preservation. This study aimed to assess feasibility and toxicity in oral cavity and maxillary sinus cancer patients. Between 2003 and 2008, 21 patients (18 male, three female; mean age 58 years; 15 patients Eastern Cooperative Oncology Group > or =1) suffering from advanced squamous cell cancers of the oral cavity (seven primaries, eight locoregional recurrences) and the maxillary sinus (six patients) were prospectively treated with three cycles of TPF (q3w) and were scheduled to undergo definitive chemoradiation. Of 21 patients, 15 (71%) could be treated with all three cycles, one patient with two cycles, and five patients with one cycle. Reasons for incomplete treatment were tumor progression, edema, seizure, bad general condition, sepsis, pneumonia (each once). The infections led to two treatment-related deaths (9.5%). Acute grade III/IV side effects were noted maximally in 11 patients (52%). Main toxicities were afebrile leukopenias and neutropenias and stomatitis. Of 15 patients, six and four patients had a clinical complete or partial remission following three cycles (67%); five patients with recurrences had no response. Ten patients underwent a definitive chemoradiation or radiation (47.6%). After a mean observation time of 17 months, nine patients are alive; one of them developed a local recurrence. Chemotherapy with TPF is a highly effective treatment with considerable toxicity that needs special expertise which is best assured in a multidisciplinary setting. Pretreated recurrent cancers demonstrated bad response. A target for organ preservation could be the maxillary sinus; due to tumor regression in advanced oral tongue cancer, consecutively, a reduced function has to be encountered.

Treatment Results and Prognostic Factors for Advanced Oral Tongue Cancer

Objective The aim of this study was to retrospectively analyze advanced oral tongue cancer to determine tumor characteristics, treatment patterns and any other prognostic factors that may influence the survival of patients with the disease. Patients and Methods The records of 70 patients with stage III to IVA oral tongue cancer (TNM system) seen between December 1999 and December 2005 at one institution were reviewed. One group of patients had been treated with surgery plus adjuvant therapy (Group A), while the other group of patients had undergone definitive concurrent chemoradiotherapy (CCRT) without surgery (Group B). The chemotherapy protocol consisted of two month ly courses of cisplatin and fluorouracil as a concurrent regimen followed by another 2-month course as an adjuvant systemic regimen. The regimen was cisplatin (20 mg/m 2/d) on day 1 and fluorouracil (1000 mg/m 2/d) on days 1 to 5. Results The 3-year overall survival, disease-free survival, local recurrence and distant metastasis rates in Groups A/B were 76%/18%, 75%/22%, 14%/33% and 13%/27%, respectively. Significant differences were observed in the overall and disease-free survival in the two groups. Multivariate analysis for predictors of overall survival across all patients, treatment types and local recurrence were significant. Furthermore, multivariate analysis to discover predictors of overall survival showed that a positive pathological finding for the margin or a margin < 1 mm in size, and extracapsular spread were significant. Conclusion Among the patients who were not candidates for surgery, the effect of definitive CCRT was not satisfactory. A higher dose of radiation was found to result in significantly better survival and local control in Group A. However, in Group B, while local control was better with higher doses, survival did not differ significantly. The effectiveness of radiotherapy might be increased with the use of brachytherapy, the use of more effective drugs such as a radiosensitizer or other recently introduced chemotherapy drugs.

Concurrent chemoradiation for locally advanced cancer of the oral tongue and base of tongue

17036 Background: Tongue cancer is rare, yet the treatment of oral and base of tongue cancer represents one of the most challenging tasks to oncologists due to the vital importance of organ preservation. For locally advanced tumors, surgery is often associated with the risk of debilitating impairment of speech and swallowing function, thus radiation has been the preferred treatment. Radiotherapy (RT) for locally advanced cancer of the oral tongue and tongue base has not been satisfactory, with a 5- year survival rate at only 20% to 40%. RT for tongue cancer is also challenged by the potential adverse effects from high dose radiation. As the treatment technology and approaches of head and neck tumors have evolved in the recent years, we report our treatment record of locally advanced tongue cancer treated in the modern era. Methods: The retrospective review was approved by institutional IRB. Our study endpoints are treatment characteristics, local tumor control, survival, preservation of swallowing function, speech, and incidence of soft tissue necrosis and osteoradionecrosis. 41 patients (pts) with locally advanced tongue cancer were treated by RT between 1996 and 2006. Median age was 58; 35/41 were male; 76% were smokers; 76% were drinkers. There were 9 stage III, 29 stage IVa and 3 stage IVb. 12 had some surgical treatment: 6 prior to RT and 6 post RT. 2/6 had positive lymph nodes post RT. Median follow-up is 32 months. All except 7 pts received concurrent chemoradiotherapy (chemoRT). Most pts except 6 had received hyperfractionated (BID) radiation treatment. Results: There were 10 recurrences. 4 pts developed 2nd primaries. Kaplan-Meier survival estimate at 5 years was 66% for pts received chemoRT, 27% for pts received RT only, and 59% for all pts. Disease-free survival at 5 years was 82% for pts received chemoRT, 21% for pts received RT only, (p=0.01 chemoRT vs RT) and 70% for all pts. PEG dependence rate declines with time. 9/41 were PEG-dependent after 9 months. All other late toxicity and functional assessment are being analyzed. Conclusions: The treatment outcome for locally advanced tongue cancer using combination chemoRT (mostly BID-RT) has resulted in much better survival and disease-free survival when compared with historical reports. PEG dependence rate continues to decline with time. No significant financial relationships to disclose.

Treatment results of continuous intra-arterial CBDCA infusion chemotherapy in combination with radiation therapy for locally advanced tongue cancer

The objective of this study was to improve the treatment results for locally advanced tongue cancer. A combination of radiotherapy with continuous intra-arterial therapy using CBDCA was used. According to TNM staging (1997), 29 patients had stage III lesions and 11 patients had stage IV (M0) lesions. A catheter was inserted through the lingual artery in 26 patients, through the external carotid artery in 11 patients, and through the faciolingual trunk in 2 patients. CBDCA was continuously infused for 4 to 6 weeks. With IA chemotherapy, external irradiation (median dose: 46.8 Gy) was simultaneously performed, and 1 to 2 courses of systemic chemotherapy were performed in 19 patients before intra-arterial chemotherapy. The 5-year local control rate was 65%. The 5-year OS rate was 39.5%. There were no clinically significant adverse side effects. Continuous IA CBDCA and concurrent radiation therapy can be delivered safely with good efficacy for locally advanced carcinoma of the tongue.

Arterial Chemoradiotherapy for Locally Advanced Tongue Cancer: Analysis of Retrospective Study of Therapeutic Results in 88 Patients

To retrospectively investigate the therapeutic results of arterial injection therapy by way of the superficial temporal artery for 88 cases of Stage III and IV (M0) tongue cancer and to clarify the factors that affected the therapeutic results. We administered intra-arterial chemoradiotherapy by continuous infusion of carboplatin in 39 patients between January 1993 and July 2002. Systemic concurrent chemotherapy was given to 19 of these patients. We administered intra-arterial chemoradiotherapy with cisplatin with sodium thiosulfate to 49 patients between October 2002 and December 2006. Concurrent systemic chemotherapy was given to 38 of these patients. The 3-year local control rate was 72% (T2-T3, 80%; and T4, 48%), and the 3-year survival rate was 57% (Stage III, 67%; Stage IV, 43%). On univariate analysis, age, T stage, N stage, overall stage, systemic chemotherapy, difference in intra-arterial chemotherapy, and performance status had a significant effect on survival. On multivariate analysis, N stage, systemic chemotherapy, difference in intra-arterial chemotherapy, and artery selected had a significant effect on survival. The therapeutic results of intra-arterial chemoradiotherapy using the superficial temporal artery were not inferior to the results of surgery. In particular, the results of arterial injection therapy using cisplatin with sodium thiosulfate were excellent, and we believe it will be a new therapy for advanced tongue cancer.

A new method of selective intra-arterial infusion therapy via the superficial temporal artery for head and neck cancer

We proposed a new selective intra-arterial infusion method via the superficial temporal artery for preventing dislocation of the catheter. This study included 92 patients who were treated by this combination therapy between May 1999 and December 2004. Primary tumor sites included the tongue in 73 patients, base of the tongue in 6 patients, floor of mouth in 4 patients, buccal mucosa in 4 patients, and other sites in 5 patients. Seventy-three patients had untreated lesions and 19 patients had recurrent lesions. Under fluoroscopy, a catheter was inserted into the target artery through the superficial temporal artery using a catheter exchange method. In 76 (83%) of 92 patients, a catheter was successfully inserted into the target artery. In 4 patients, the catheter fell out of the selected artery during treatment. This selective intra-arterial method will be an important modality for advanced tongue cancer.

Reconstruction of the tongue using an extended vertical lower trapezius island myocutaneous flap after removal of advanced tongue cancer

In this study we explored an effective method to repair defects in the tongue that had been produced during removal of advanced tongue cancer. Eighteen patients with advanced squamous cell carcinoma of the tongue were treated, and extended vertical lower trapezius island myocutaneous flaps based on the transverse cervical artery were used to repair more than half the tongue. No flap failed completely and no shoulder was affected. The lingual contours were excellent. The functional results in terms of speech and swallowing were satisfactory. The patients were followed up for 6 to 24 months. Three of them were alive with disease and two have died of the local recurrence or metastasis at 18 and 20 months, respectively. The extended vertical lower trapezius island myocutaneous flap is a large, simple, and reliable flap, which is preferred for reconstruction of defects of the tongue after removal of advanced tongue cancer.

The surgical management and speech and swallowing rehabilitation of patients with advanced tongue cancer in South Africa

Advanced tongue cancer may have a devastating effect on a person’s ability to speak and to swallow. Very little is known about the surgical management and speech and swallowing rehabilitation of persons with advanced tongue cancer in South Africa.&#x0D; &#x0D; Opsomming&#x0D; Gevorderde tongkanker het ‘n geweldige impak op ‘n persoon se vermoë om te praat en te sluk. Baie min inligting is bekend oor die chirurgiese behandeling en spraak- en slukrehabilitasie van persone met gevorderde tongkanker in Suid-Afrika.&#x0D; &#x0D; *Please note: This is a reduced version of the abstract. Please refer to PDF for full text.

Combined repair of large defect caused by radical surgery of advanced tongue cancer with rib-major pectoralis myocutaneous flap carrying costal parietal pleura

To explore the clinical value and safety of using rib-major pectoralis myocutaneous flap carrying costal parietal pleura in combined repair of large soft and hard tissue defect caused by radical surgery of advanced tongue cancer. Six patients with advanced tongue carcinoma involving the floor of mouth and mandible were performed combined radical neck dissection with glossectomy and mandibulectomy, which caused large soft and hard tissue defect. Six rib-major pectoralis myocutaneous flaps carrying costal parietal pleura were transferred for immediate repair of the large defects. The rib flaps were applied for the repair of mandible, and the major pectoralis myocutaneous flaps were applied for the reconstruction of tongue and floor of mouth. Six patients recovered well after operation. Six rib-major pectoralis myocutaneous flaps carrying costal parietal pleura survived well; the wounds of surgical incision of the oral cavity, neck, and chest healed up. The reconstructed tongue and the lower face appearance were satisfactory, the occlusion relationships were normal; the speaking as well as swallowing functions recovered. It's safe and reliable to use rib-major pectoralis myocutaneous flap carrying costal parietal pleura to repair large soft and hard tissue defect in oral and maxillofacial region. Opening pleural cavity and harvest costal parietal pleura would not influence patients' thoracic movement and breath function and would not cause other complications. It's simple and safe for harvesting the composite flap. Carrying costal parietal pleura assures the sufficient blood supply of rib in the composite flap.

Usefulness of omental tissue as a filler material in patients with dysphagia following a resection of advanced tongue cancer

Usefulness of omental tissue as a filler material in patients with dysphagia following a resection of advanced tongue cancer

舌癌治療成績の検討

We retrospectively reviewed 52 tongue cancer patients who received definitive treatment at Shiga University Hospital between January 1993 and August 2004.In cases of T1and early T2 (early T2: ≤3cm), partial glossectomy was performed. Radical operation followed by reconstructive surgery was performed after pre-operative chemotherapy in cases of advanced T2 (advanced T2: >3cm), T3 and T4. Post-operative radiation was performed in some cases to prevent local and cervical recurrence.The 5-year survival rates by the Kaplan-Meier method were 92% in stage I, 88% in stage II, 73% in stage III, 55% in stage IV, and 72% overall, respectively. The 5-year survival rates by the size in T2 cases were 90% in early T2 and 46% in advanced T2. Twelve cases were relapsed. Locoregional recurrence occurred in 11 patients (5 cases at the primary site, 6 in the neck), and distant metastasis in 4 patients. Long-term survivors after secondary treatment were 3 of 11 cases with recurrence at the primary site.The results of salvage treatment for recurrent cases were discouraging. Adjuvant chemotherapy and post-operative radiotherapy are recommended for advanced tongue cancer.

Diffuse expression of laminin γ2 chain in disseminating and infiltrating cancer cells indicates a highly malignant state in advanced tongue cancer

The expression of laminin (LN)gamma2 chain in the primary lesions of 20 patients with advanced tongue cancer was analyzed. Positive expressions of LNgamma2 were noted in all of the primary tissue specimens, however, the expression patterns clearly differed according to the mode of growth and invasion of cancer cells. In tumor nests where cancer cells preserved cell-cell adhesiveness and showed polar differentiation, LNgamma2 was expressed only in the peripheral cells of the tumor nests; peripheral expression. On the other hands when cancer cells diminished their cell-cell adhesiveness and strongly infiltrated through stroma, almost all of the cancer cells diffusely expressed LNgamma2; diffuse expression. The peripheral expression of LNgamma2 were noted in 13 patients and the diffuse expressions were noted in 7 patients. The rates of positive cervical metastases according to the expression type were 7/13 for the peripheral expression and 7/7 for the diffuse expression (p = 0.02). The diseases specific 3-year survival rates for the patients with the peripheral expression and the diffuse expression were 68% and 14%, respectively (p = 0.02). The diffuse expression of LNgamma2 in the disseminating and infiltrating cancer cells might indicate a highly malignant state in advanced tongue cancer. Therefore, a more intensive treatment modality would be necessary for the patients with advanced tongue cancer showing the diffuse LNgamma2 expression.

Rapid superselective high-dose cisplatin infusion and high-dose rate radiotherapy for advanced tongue cancer

Rapid superselective high-dose cisplatin infusion and high-dose rate radiotherapy for advanced tongue cancer

L-34 The surgical treatment of advancedtongue cancer

L-34 The surgical treatment of advancedtongue cancer

Prognostic significance of biomarkers in squamous cell carcinoma of the tongue: multivariate analysis.

Expression of a panel of biomarkers, such as p53, Bcl-2, Cyclin D1, c-myc, p21ras, c-erb B2, cytokeratin-19 (CK-19), and factor VIII-related antigen (FVIII-RA), was studied together in anterior tongue tumors from the oral cavity and in posterior tongue tumors from the oropharynx of patients with early- and locally advanced-stage disease, to evaluate their prognostic value. The expression of the above-mentioned biomarkers was studied by immunohistochemical localization. In this study, 18%, 26%, 62%, 75%, 73%, 50%, and 29% of the tumors exhibited p53, Bcl-2, Cyclin D1, c-myc, p21ras, c-erb B2, and CK-19 expression, respectively. Twenty percent of the tumors had a microvessel count of >0.0. The expression of these biomarkers was also correlated with clinicopathologic parameters. In early-stage patients with a tobacco habit, who showed borderline significance for relapse-free survival by Kaplan-Meier survival analysis, this turned out to be significant, with the general linear model univariate survival analysis. In the total group, disease stage emerged as the most significant prognostic factor, followed by c-myc, when Cox forward stepwise regression and general linear model multivariate survival analysis were performed. However, Cyclin D1, which was significant by Cox forward stepwise regression analysis, lost its significance by general linear model multivariate analysis. In patients with early-stage disease, MVC, which was a significant predictor of disease relapse by Cox forward stepwise regression analysis, lost its significance by general linear model analysis because of small number of patients. In patients with locally advanced tongue cancer, multivariate survival analysis of individual biomarkers by both Cox forward stepwise regression and general linear model analysis indicated c-myc expression to be strongly indicative of poor prognosis. However, multivariate analysis of individual markers along with a combination of markers showed that only by Cox forward stepwise regression analysis did the combined expression of markers c-myc, Cyclin D1, and p21ras emerge as a significant independent prognosticator. Overall stage emerged as the most significant prognostic indicator of disease outcome. Tobacco habit also affected relapse-free survival in patients with early-stage disease. However, immunostaining of c-myc in the tumors of locally advanced-stage tongue cancer patients might be a potential adjunct to clinical stage in the pathologic evaluation of tongue specimens.

Medical cost analysis of neoadjuvant chemotherapy for advanced tongue and oropharyngeal cancer

We performed a medical cost analysis on the use of neoadjuvant chemotherapy (NAC) in multi-modal treatments for advanced tongue and oropharyngeal cancer. Twenty-two patients with stage III and IV squamous cell carcinoma of the tongue and oropharynx were enrolled in this study. Two courses of NAC with CDDP and 5-FU followed by radiotherapy were performed in 13 patients who showed a partial response or a complete response after the first course of NAC. The doses of radiation were 60 Gy for 4 patients (rad. group), and 72 Gy for 9 patients who received hyperfractionated radiotherapy with simultaneous Carboplatin (HF rad. group). Radical surgery was performed in 9 patients who did not respond to NAC (surg. group). The mean duration of hospital stay was 89.3 days for the rad. group, 92.0 days for the HF rad. group, and 113.3 days for the surg. group. The mean medical cost was 238,700 points for the rad. group, 264,846 points for the HF rad. group, and 459,468 points for the surg. group. The mean amounts and percentages of cost for NAC were 39,473 points and 16.1% for the rad. group, 44,802 points and 16.9% for the HF rad. group, and 23,451 points and 5.1% for the surg. group. The mean amounts of cost for NAC including examination costs and nursing costs for chemotherapy were 130,196 points and 54.5% for the rad. group, 150,046 points and 55.7% for the HF rad. group, and 113,839 points and 24.8% for the surg. group. The cost of NAC accounted for half of the total cost of chemo-radiation treatment for functional preservation. The duration of the hospital stay was prolonged by NAC, which accounted for a quarter of the total cost for the surg. group. Survival benefits are considered in the analysis of treatment cost-effectiveness for head and neck cancers. In the future, QOL, which is defined as the utility achieved as a result of multi-modal treatments, should also be analyzed along with survival benefits. Cost-utility analyses should include quality-adjusted life years, based upon the cost identification results of our analysis for NAC, to evaluate the efficacy of NAC in multi-modal treatments for head and neck cancers.