Induction Toripalimab and Chemotherapy for Organ Preservation in Locally Advanced Laryngeal and Hypopharyngeal Cancer: A Single-Arm Phase II Clinical Trial.

PURPOSE: The aim of this study was to assess the efficacy, toxicities, and potential role of larynx preservation of induction chemotherapy combined with programmed cell death protein 1 (PD-1) inhibitor in locally advanced laryngeal and hypopharyngeal cancer. PATIENTS AND METHODS: This is a single-arm phase II study. Patients with histopathologically confirmed, resectable locally advanced laryngeal/hypopharyngeal squamous cell carcinoma and Eastern Cooperative Oncology Group Performance Status 0-1 were eligible. Three cycles of induction chemotherapy (paclitaxel 175 mg/m2 d1, cisplatin 25 mg/m2 d1-3) combined with PD-1 inhibitor (toripalimab 240 mg d0) were administered. Response assessment was performed after induction chemoimmunotherapy using RECIST 1.1 criteria. Patients with a complete/partial response of the primary tumor received concurrent chemoradiation, followed by maintenance therapy of toripalimab. Otherwise, patients were referred to surgery, followed by adjuvant (chemo) radiation and maintenance therapy of toripalimab. The primary endpoint is a larynx preservation rate at 3 months postradiation. RESULTS: Twenty-seven patients were enrolled. Most cases exhibited stage IV disease (81.5%), with T4 representing 37.0%. Five patients underwent pretreatment tracheostomy because of impaired larynx function. Overall response rate of induction chemoimmunotherapy was 85.2%. At 3 months postradiation, the larynx preservation rate was 88.9%. With a median follow-up of 18.7 months, the 1-year overall survival rate, progression-free survival rate, and larynx preservation rate were 84.7%, 77.6%, and 88.7%, respectively. When excluding those with pretreatment tracheostomy, the 1-year larynx preservation rate was 95.5%. Exploratory analysis revealed that relapse correlated with enrichment of RNA signature of hypoxia and M2 macrophage-associated genes. CONCLUSIONS: Induction toripalimab combined with chemotherapy provided encouraging activity, promising larynx preservation rate and acceptable toxicity in this cohort of extensively locally advanced laryngeal and hypopharyngeal cancer.

Photothermal treatment with EGFRmAb-AuNPs induces apoptosis in hypopharyngeal carcinoma cells via PI3K/AKT/mTOR and DNA damage response pathways.

Hypopharyngeal carcinoma (HC) is one of the most malignant tumors in the upper aerodigestive tract. Currently, there are no effective treatments for HC. Gold nanoparticles (AuNPs) are a promising tool that can be used for plasmonic photothermal therapy (PPTT), which refers to the use of electromagnetic radiation, most often in near infrared (NIR) region, for the treatment of various medical conditions including cancer. AuNPs have been proved to be a promising tool for NIR spectroscopy-mediated photothermal therapies. In this study, we chemically conjugated AuNPs with a monoclonal antibody (mAb) targeting the epidermal growth factor receptor (EGFR), a cell-surface receptor that is overexpressed in many cancers. We then assessed the effect of NIR photothermal treatment with the EGFRmAb-AuNPs in FaDu HC cells. Our data showed that nanoparticle conjugation with the EGFRmAb improved the specific targeting towards FaDu cells and reduced cytotoxicity towards normal (293 T) cells which do not overexpress the EGFR. A significant amount of our EGFRmAb-conjugated AuNPs could enter the nucleus. Moreover, the expression levels of double strand DNA break repair proteins, including p-ATR, p-CHK1, and p-CHK2 were increased following AuNPs treatment, indicating the presence of DNA damage. These findings suggest that the AuNPs can potentially disrupt genome integrity and induce apoptosis. In addition, EGFRmAb-AuNPs+NIR could induce FaDu cell apoptosis, accompanied by the inhibition of the PI3K/AKT/mTOR pathway and stimulation of DNA damage response. Based on these data, PPTT using the EGFRmAb-AuNPs could be a new promising treatment for HC.

Long-term Results of a Multicenter Randomized Phase III Trial of Induction Chemotherapy With Cisplatin, 5-fluorouracil, ± Docetaxel for Larynx Preservation.

BACKGROUND: The purpose of GORTEC 2000-01 was to compare the long-term efficacy and safety of induction chemotherapy with cisplatin (P) and 5-fluorouracil (F) with or without docetaxel (T) for larynx preservation. METHODS: Operable patients with untreated stage III or IV larynx or hypopharynx invasive squamous cell carcinoma who required total laryngectomy were randomly assigned to three cycles of induction chemotherapy with either TPF or PF, followed by radiation therapy for responders. The primary endpoint was three-year larynx preservation rate. Secondary endpoints included larynx dysfunction-free survival (LDFFS), overall survival (OS), disease-free survival (DFS), loco-regional control rate (LCR), cause of death, and later toxicity rates. Survival and other data were analyzed by Kaplan-Meier methods. All statistical tests were two-sided. RESULTS: Two hundred thirteen patients were treated with median follow-up of 105 months. The five- and 10-year larynx preservation rates were 74.0% (95% CI = 0.64 to 0.82) vs 58.1% (95% CI = 0.47 to 0.68) and 70.3% (95% CI = 0.58 to 0.8) vs 46.5% (95% CI = 0.31 to 0.63, P = .01) in the TPF vs PF arm, respectively. The five- and 10-year LDFFS rates were 67.2% (95% CI = 0.57 to 0.76) vs 46.5% (95% CI = 0.36 to 0.57) and 63.7% (95% CI = 0.52 to 0.74) vs 37.2% (95% CI = 0.24 to 0.52, P = .001), respectively. OS, DFS, and LCR were not statistically improved in the TPF vs the PF arm. Statistically fewer grade 3-4 late toxicities of the larynx occurred with the TPF regimen compared with the PF arm (9.3% vs 17.1%, G-test, P = .038). CONCLUSION: Long-term follow-up confirms that induction chemotherapy with TPF increased larynx preservation and larynx dysfunction-free survival. In this larynx preservation approach using induction chemotherapy, TPF should be recommended, followed by radiation therapy.

Oncologic results of transoral laser microsurgery for squamous cell carcinoma of the posterior pharyngeal wall.

BACKGROUND: The purpose of this study was to evaluate oncologic outcomes of transoral laser microsurgery (TLM) in patients with cancer of the oropharyngeal and/or hypopharyngeal posterior wall. METHODS: Between August 1986 and December 2006, 25 patients (oropharyngeal n = 12; hypopharyngeal n = 13) were treated by primary CO2 laser microsurgery. Treatment was exclusively TLM with or without selective neck dissection in 12 cases (48%); TLM with adjuvant (chemo)radiotherapy was performed in 13 cases (52%). RESULTS: Data were analyzed by using the Kaplan-Meier method. The median follow-up was 41.6 months. The 5-year overall, recurrence-free, and disease-specific survival rates for stages I/II were 36,5%, 60,0%, and 87,5% and for stages III/IVa 41,2%, 36,4%, and 56,3%, respectively. CONCLUSION: With respect to local control and survival, results are comparable to conventional surgery.

[A case report of the difficulty treating an endstage oncologic ENT patient with parenteral nutrition]. / Ein Fallbericht über die Problematik der Ernährung am Lebensende eines onkologischen HNO-Patienten.

The occurrence of cachexia at the end of life of patients suffering from cancer is a common seen problem. Within the last years new definitions, diagnostic criteria and classification systems of cachexia have been developed to improve the clinical practice. Still therapeutic interventions are limited; the role of parenteral nutrition (PN) remains controversial. PN cannot be generally recommended in patients with incurable malignancies, not even in ill-nourished patients with inadequate oral or enteral nutrition due to a changed metabolism. Treating a cachectic endstage patient suffering from head-neck-cancer we were faced with different problems.

[Magnesium premedication prevents Cisplatin-induced nephrotoxicity in patients with esophageal and hypopharyngeal cancer].

Hypomagnesemia is one of the well-known side effects in patients receiving cisplatin-containing chemotherapy. However, the relevance between hypomagnesemia and cisplatin-induced nephrotoxicity remain to be completely elucidated. Although patients with esophageal and hypopharyngeal cancer are susceptible to dehydration, there is no evidence yet that magnesium supplementation for these patients will prevent nephrotoxicity during cisplatin-containing chemotherapy. The aim of this study was to examine the effect of magnesium supplementation on the prevention of cisplatin-induced nephrotoxicity for patients with esophageal and hypopharyngeal cancer. Twenty-three patients with esophageal or hypopharyngeal cancer were studied over 2 weeks. Ten of them received magnesium supplementation and 13 did not. Magnesium sulphate(20 mEq) was administered before 5-fluorouracil(800mg/m2/24 h/day 1-5)and cisplatin(80mg/m2/day 1)(FP)treatment. The maximum serum creatinine concentration of magnesium-supplemented group demonstrated a significantly lower concentration compared to the non-magnesium-supplemented group(p=0. 018). As a result, magnesium supplementation successfully reduced the incidence rate of nephrotoxicity(p=0. 038). These results showed that magnesium supplementation before FP treatment may be quite beneficial for preventing nephrotoxicity in patients with esophageal and hypopharyngeal cancer, and it is therefore recommended that magnesium be routinely supplemented during FP treatment for esophageal or hypopharyngeal cancer.

Necessity of routine ipsilateral hemithyroidectomy during laryngopharyngectomy for pyriform sinus cancer.

PURPOSE: The aim of this study was to revisit the role of hemithyroidectomy in the treatment of pyriform sinus cancer by determining the incidence of thyroid gland invasion by the tumor. MATERIALS AND METHODS: Medical records of 27 patients with pyriform sinus cancer who underwent laryngopharyngectomy with ipsilateral hemithyroidectomy from 1999 to 2010 at a National Cancer Institute-designated comprehensive cancer center were retrospectively reviewed. Computed tomographic scans of the neck, operative notes, and surgical specimens were examined to determine the presence of thyroid gland invasion by imaging, clinical appearance, and pathology. RESULTS: There were 19 male and 8 female patients (age range, 44-79 years; mean, 59.9 years). Most of the cases (85%) had advanced-stage disease. Extralaryngeal spread of tumor with thyroid cartilage invasion was noted in the computed tomographic scans of 5 patients; however, there was no radiologic evidence of thyroid gland invasion in any patient. No gross thyroid gland invasion by the tumor was appreciated in any patient during surgery. No histologic evidence of tumoral invasion of the thyroid gland was found in any of 27 surgical specimens. CONCLUSIONS: Results of this study suggest that thyroid gland invasion by pyriform sinus cancer is not common. Therefore, a routine ipsilateral hemithyroidectomy may not be necessary in the treatment of every patient with pyriform sinus cancer, unless there is evidence of thyroid gland invasion.

Prospective trial of chemotherapy-enhanced accelerated radiotherapy for larynx preservation in patients with intermediate-volume hypopharyngeal cancer.

BACKGROUND: Altered fractionation radiotherapy (RT) improves locoregional control in head and neck cancer without aggravation of late adverse events. To improve successful larynx-preservation rates in patients with resectable, intermediate-volume hypopharyngeal cancer, a prospective trial of chemotherapy-enhanced accelerated RT was conducted. METHODS: Patients with T2 to T4 hypopharyngeal cancer received 40 Gray (Gy)/4 weeks to the entire neck followed by boost RT administering 30 Gy/2 weeks (1.5 Gy twice-daily fractionation). Cisplatin and 5-fluorouracil were administered concomitantly only during boost RT. RESULTS: Thirty-five patients were enrolled in this study. All patients completed this protocol as planned. After a median follow-up period for surviving patients of 59 months (24-90 months), overall survival and local control rates at 3 years were 91% (95% confidence interval, 81% to 100%), and 88% (79% to 99%), respectively. All surviving patients maintained normalcy of diets. CONCLUSION: This regimen was feasible with encouraging oncological and functional outcomes.

Loss of heterozygosity of tumor suppressor genes (p16, Rb, E-cadherin, p53) in hypopharynx squamous cell carcinoma.

OBJECTIVE: Microsatellite alterations, especially those that cause loss of heterozygosity (LOH), have recently been postulated as a novel mechanism of carcinogenesis and a useful prognostic factor in many kinds of malignant tumors. However, few studies have focused on a specific site, hypopharynx. The aim of this study was to evaluate the relationship between LOH and hypopharyngeal squamous cell carcinoma (HPSCC). STUDY DESIGN: Laboratory-based study. SETTING: Integrated health care system. SUBJECTS AND METHODS: Matched normal and cancerous tissues from 30 patients with HPSCC were examined for LOH in 4 tumor suppressor genes (TSGs) (p16, Rb, E-cadherin, and p53) at loci 9p21, 13q21, 6q22, and 17p13, respectively, using microsatellite markers amplified by polymerase chain reaction. The results for each loci were compared with clinicopathological features. RESULTS: Among the 30 cases, 26 (86.7%) exhibited LOH, with the most common alteration being LOH at p53 (52.6%). Significantly higher rates of LOH detection were seen in Rb, p53, and the LOH-high group (cases where 2 or more loci with LOH were found) in cases of lymph node metastasis. Compared with stage I and II carcinoma, tumors of stages III and IV had significantly higher frequencies of LOH in Rb, p53, and the LOH-high group. However, the presence of LOH was not significantly correlated with survival. CONCLUSION: These results suggest that LOH in TSGs such as Rb and p53 may contribute to the development and progression of HPSCC. The presence of LOH in the primary tumor may also be predictive of lymph node metastasis.

When to manage level V in head and neck carcinoma?

OBJECTIVES/HYPOTHESIS: As superselective neck dissection strategy is gaining popularity to minimize postoperative morbidity and better life quality, we investigated the metastatic nodal status of level V neck lymph node group for head and neck squamous cell carcinoma in various primary sites. We have also aimed to display the impact of involvement of other nodal groups on level V. STUDY DESIGN: Retrospective review of histopathologic examination of case series at a comprehensive cancer center. METHODS: The study group was composed of 107 patients who underwent a type of neck dissection including level V among 243 patients. The impact of primary site and metastatic nodal status of other levels on metastasis to level V involvement were evaluated. RESULTS: The most common primary tumor site was oropharynx (n = 43), followed by oral cavity (n = 32), larynx (n = 16), carcinoma of unknown primary (n = 10), and hypopharynx (n = 6). General pathologic N positivity for all levels was 78.3% (76 of 97) when 10 carcinoma of unknown primary patients were excluded. Level V was involved in 13 of 107 (12.1%) patients. Level V was not involved in any patient when the other levels were not involved (0 of 21). Even when considering only N+ patients, the ratio of N positivity for level V is still <20% (13 of 86, 15.1%). CONCLUSIONS: Because level V was not involved in any patient when the other levels were not involved, it might be reasonable to preserve level V especially in clinically and intraoperatively N0 patients.

Long-term survival of induction chemotherapy plus surgery and postoperative radiotherapy in patients with stage IV hypopharyngeal cancer.

This study was conducted to evaluate the safety, efficacy, and tolerability of induction chemotherapy plus surgery and postoperative radiotherapy in patients with stage IV hypopharyngeal cancer. The patients received two to three cycles of induction chemotherapy before surgery, with cisplatin (100 mg/m(2)) by rapid intravenous (i.v.) infusion over 15-20 min on day 1, bleomycin (10 mg/m(2)) on days 1 and 5, and 5-fluorouracil (800 mg/m(2)/day) by continuous i.v. infusion on days 1 through 5, repeated every 21 days. Adjuvant radiotherapy was begun 4-6 weeks after surgery. From July 1999 to December 2004, a total of 52 patients were enrolled. After completion of two to three courses of induction chemotherapy, 22 cases of CR (complete response) and 16 cases of PR (partial response) in the primary site were confirmed, giving an overall response rate (ORR) of 73.1% [95% confidence interval (CI), 61.1-85.2%]. There were 17 CRs and 19 PRs in neck lymph nodes, giving an ORR of 69.2%. The combined primary tumor site and lymph node response was 17 CRs and 16 PRs, giving an ORR of 63.5% (95% CI, 50.4-76.6%). The median time to progression and overall survival for all the patients were 32 months (95% CI, 7.6-56.4 months) and 36 months (95% CI, 22.3-49.7 months), respectively. The estimate of time to progression and overall survival at 5 years was 24.5% (95% CI, 12.5-36.5%) and 35.9% (95% CI, 23.2-48.6%), respectively. In conclusion, induction chemotherapy plus surgery and postoperative radiotherapy is a treatment modality that is tolerated with encouraging activity and survival outcome in patients with stage IV hypopharyngeal cancer.

When to address level I lymph nodes in neck dissections?

OBJECTIVE: To investigate the involvement of level I neck lymph node groups in head and neck carcinoma and compare the effect of primary tumor sites, such as oral cavity (OC), oropharynx (OP), hypopharynx (HP), and larynx (Lx), on level I lymph node metastasis. STUDY DESIGN: Case series with chart review. SETTING: Comprehensive Cancer Center. SUBJECTS AND METHODS: A total of 243 patients with OC and laryngopharyngeal carcinoma who underwent neck dissections in the last three years were included in the study. The primary tumor site was OC, followed by OP, Lx, HP, and carcinoma of unknown primary (CUP). RESULTS: Level I was involved in 29 of 243 (11.9%) patients. The other levels were also positive in all but five (17.2%) level I-involved patients. The primary tumor site with level I lymph node metastasis was OC (19.1%), followed by CUP (11.1%), OP (9.8%), Lx (4.4%), and HP (0%). The Lx primary site involved level I only if there were multiple other adverse prognostic features, such as N3 neck, extracapsular spread, pathologic involvement of all resected lymph nodes, involvement of all levels I-V, and invasion of the submandibular gland. CONCLUSION: Although the submandibular content is resected as part of radical and modified radical neck dissections, level I-sparing selective neck dissections could be a safe and effective surgical neck management strategy in appropriately selected patients with OP, Lx, and HP carcinoma.

Sequential therapy for the locally advanced larynx and hypopharynx cancer subgroup in TAX 324: survival, surgery, and organ preservation.

BACKGROUND: Locally advanced laryngeal and hypopharyngeal cancers (LHC) represent a group of cancers for which surgery, laryngectomy-free survival (LFS), overall survival (OS), and progression-free survival (PFS) are clinically meaningful end points. PATIENTS AND METHODS: These outcomes were analyzed in the subgroup of assessable LHC patients enrolled in TAX 324, a phase III trial of sequential therapy comparing docetaxel plus cisplatin and fluorouracil (TPF) against cisplatin and fluorouracil (PF), followed by chemoradiotherapy. RESULTS: Among 501 patients enrolled in TAX 324, 166 had LHC (TPF, n = 90; PF, n = 76). Patient characteristics were similar between subgroups. Median OS for TPF was 59 months [95% confidence interval (CI): 31-not reached] versus 24 months (95% CI: 13-42) for PF [hazard ratio (HR) for death: 0.62; 95% CI: 0.41-0.94; P = 0.024]. Median PFS for TPF was 21 months (95% CI: 12-59) versus 11 months (95% CI: 8-14) for PF (HR: 0.66; 95% CI: 0.45-0.97; P = 0.032). Among operable patients (TPF, n = 67; PF, n = 56), LFS was significantly greater with TPF (HR: 0.59; 95% CI: 0.37-0.95; P = 0.030). Three-year LFS with TPF was 52% versus 32% for PF. Fewer TPF patients had surgery (22% versus 42%; P = 0.030). CONCLUSIONS: In locally advanced LHC, sequential therapy with induction TPF significantly improved survival and PFS versus PF. Among operable patients, TPF also significantly improved LFS and PFS. These results support the use of sequential TPF followed by carboplatin chemoradiotherapy as a treatment option for organ preservation or to improve survival in locally advanced LHC.

[Current role for induction chemotherapy in head and neck tumors]. / Stellenwert der Induktionstherapie bei Kopf-Hals-Tumoren.

According to recent publications in the New England Journal of Medicine (TAX323, TAX324) of the study groups around Jan Vermorken and Marshall Posner induction chemotherapy in squamous cell carcinomas of the head-neck area (in the closer: Oro-hypopharynx, oral cavity and larynx) currently seems to generate a worldwide renaissance. Renaissance, because in the last few decades, induction chemo therapy in this group of tumors after lack of survival improvement in the vast majority of studies was again abandoned. The new data raise the question for which entities induction chemo therapy can be recommended (actually, a combination of docetaxel, cisplatin and 5-fluorouracil; TPF)? The unbroken high value of primary surgery with adjuvant radiation or chemo radiation was complementary to primary radio chemotherapy for non resectable tumors until today worldwide. Running studies are sorting out the role of induction chemotherapy in the current context of clarifying optimal multimodal treatment.

Multimodal intensification regimens for advanced, resectable, previously untreated squamous cell cancer of the oral cavity, oropharynx, or hypopharynx: a 12-year experience.

OBJECTIVE: To determine the feasibility of, compliance with, and long-term survival with intensification treatment regimens for patients with advanced, resectable, previously untreated head and neck squamous cell carcinoma. DESIGN: Prospective phase 2 clinical trial (3 similar, consecutively evolved trials). SETTING: Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University. PATIENTS: One hundred twenty-three patients (median age, 60 years; range, 30-78 years) with previously untreated, resectable, advanced squamous cell carcinomas of the oral cavity, oropharynx, or hypopharynx. INTERVENTIONS: Perioperative cisplatin chemoradiotherapy, surgical resection with intraoperative radiotherapy, and postoperative paclitaxel and cisplatin chemoradiotherapy. MAIN OUTCOME MEASURES: The feasibility, compliance, and long-term survival associated with the 3 intensification regimens. RESULTS: Compliance with all 3 intensification regimens averaged 61% (75/123). Patient-directed noncompliance occurred in 16 patients (13%). The average locoregional (112/123, 91%) and systemic (106/123, 86%) disease control rates were excellent. Overall long-term disease-specific survival was 73%. Median time at risk was 62.5 months (range, 1 day to 100.4 months). CONCLUSIONS: The intensification regimens result in excellent disease control rates and long-term survival in this particular patient population. Future evolution of these regimens will include some modifications to further decrease toxic effects followed by phase 2 multi-institutional trials to determine whether the single-institutional experience can be duplicated. The results of these studies will determine whether phase 3 trials can be proposed.

[Transpupillary thermotherapy for choroidal metastases]. / Chorioidealis metastasisok transpupillaris termoterápiája.

PURPOSE: To present three cases with choroidal metastases treated with transpupillary thermotherapy (TTT). PATIENTS AND METHODS: Five choroidal metastases of three patients were treated with infrared laser thermotherapy (TTT). In all cases the distorted vision, caused by serous retinal detachment joining the posterior pole metastasis, led the patients to an ophthalmologist. In our first case an intraductal breast carcinoma led to bilateral multifocal choroidal metastases. In the second case a squamous cell carcinoma of the hypopharynx caused a rapidly growing choroidal metastasis. The primary tumor of the third patient was urothelial carcinoma. The efficacy of treatment and systemic (general health) outcomes are discussed. RESULTS: Three of the tumors regressed to a flat scar, and led to improved vision after one session of treatment, one tumor needed two sessions of treatment to regress. The metastasis from the squamous cell carcinoma grew very fast and caused an early death not allowing follow-up. CONCLUSIONS: TTT can be a safe therapeutic option for small choroidal metastases. This one-session treatment leads to tumor regression, improves vision and positively affects quality of life of the patient suffering from metastatic cancer.

Induction chemotherapy with cisplatin and 5-fluorouracil followed by chemoradiotherapy or radiotherapy alone in the treatment of locoregionally advanced resectable cancers of the larynx and hypopharynx: results of single-center study of 45 patients.

BACKGROUND: Induction chemotherapy with cisplatin and fluorouracil and radiotherapy is an effective alternative to surgery in patients with carcinoma of the larynx and hypopharynx who are treated for organ preservation. METHODS: We designed a protocol to evaluate the possibility of organ preservation in patients with advanced, resectable carcinoma of the larynx and hypopharynx. Forty-five eligible patients who were followed up between April 1999 and May 2001 were enrolled. Initially, these patients were treated with two cycles of induction chemotherapy consisting of cisplatin, 20 mg/m2/day on days 1 to 5, and 5-fluorouracil, 600 mg/m2/day by continuous infusion on days 1 to 5. Patients who had a complete response to chemotherapy were treated with definitive radiotherapy; patients who had a partial response to chemotherapy were treated with chemoradiotherapy. Cisplatin, 35 mg/m2/week, was introduced throughout the duration of radiotherapy. Patients who had no response or progressive disease underwent surgery with postoperative radiotherapy. Patients with N2 or N3 positive lymph nodes underwent neck dissection after the treatment. RESULTS: The mean age was 56.6 years (range, 34-75 years). The overall response rate to induction chemotherapy was 71.1%, with a 17.8% complete response rate and 53.3% partial response rate. With a median follow-up of 13.7 months, 23 (51.1%) of all patients and 63.3% of surviving patients have had a preservation of the larynx or hypopharynx and remain disease free. The most common toxicities were nausea and vomiting and mucositis. CONCLUSION: Organ preservation, with multimodality treatment, may be achievable in some of the patients with resectable, advanced larynx or hypopharynx cancers without apparent compromise of survival.

[Treatment of hypopharyngeal carcinomas--an institutional analysis of the results of FAR radiochemotherapy, radical resection, and free jejunum flap reconstruction and the indication of neck dissection].

The treatment results of 65 patients with hypopharyngeal carcinomas treated at our institute between 1995 and 2000 were analyzed. In general, concurrent radiochemotherapy (RCT), consisting of intravenous 5-FU injection, intra-muscular vitamin A injection, and radiation (FAR therapy) was used as an initial treatment for advanced hypopharyngeal carcinomas and early hypopharyngeal carcinomas. Tumor responses were evaluated at the time of radiation doses of 30Gy. Patients who showed a complete response (CR) subsequently received curative radiation doses of 60 to 70Gy. Patients who did not show a CR underwent radical surgery consisting of pharyngo-laryngo-cervical esophagectomy, neck dissection for positive cervical nodes and/or the primary tumor sides, and reconstruction using a free jejunum flap. The disease-specific 5-year survival rates were 92%, 55%, 35% and 49% for stage I/II, III, IV and all cases, respectively. Eight out of 9 patients with stage I/II disease who showed a CR after receiving 30Gy of RCT survived with an intact larynx after definitive RCT. All the patients with stage II/III disease who underwent radical surgery after receiving 30Gy of RCT did not have a recurrence, whereas the 5-year survival rate of patients with stage IV disease who underwent RCT and radical surgery was 45%. Seventeen out of 19 patients with clinically negative cervical nodes on the opposite side of their primary tumors showed no nodal metastasis after RCT without neck dissection. This result suggests that elective neck dissection after RCT is not necessary. To improve the treatment results for hypopharyngeal carcinomas, early detection of this disease is prerequisite. In addition, the clinical diagnosis of highly malignant cases and new molecular-targeted therapies based on an analysis of distant metastasis mechanisms should be developed to overcome the poor prognosis of advanced hypopharyngeal carcinomas.

Preservation of form and function during management of cancer of the larynx and hypopharynx.

The treatment of laryngeal and hypopharyngeal cancer has seen notable changes during the twentieth century. Intensive surgical research has allowed laryngologists to deal with almost any local extension and to propose an appropriate surgical procedure for each case. This surgery is able to control the disease in most patients locally but is limited in its indications (resectable diseases and operable patients). On the other hand, radiotherapy has been impressively improved (dosimetry, definition of target volume) and has become an indisputable alternative to surgery. The two approaches are comparable in terms of local control and functional results when dealing with early disease. For advanced disease, however, the debate is open between surgery, which is more efficient but mutilating, and radiotherapy, which can preserve the larynx in many instances even though it requires sometimes mutilating surgery for salvage. The appearance of platinum-based chemotherapy has updated this discussion. To date, most of the randomized comparisons of mutilating/nonmutilating approaches have been with induction chemotherapy followed by irradiation if there has been a good clinical response to the chemotherapy. There are other options as well that deserve evaluation (e.g., radiotherapy with altered fractionation or with concurrent chemotherapy), although surgery still seems to be indicated in certain cases. Finally, efforts should be made to select patients properly (based on tumor characteristics, clinical aspects, imaging, and biology) for the various strategies with the primary goal of curing the patient and secondarily to preserve laryngeal form and function when possible.