[Proposal for the selection and delineation of clinical target volumes for the radiotherapy of submandibular gland tumours]. / Proposition de sélection et délinéation des volumes cibles anatomocliniques tumoraux et ganglionnaire pour la radiothérapie des cancers de la glande sous-mandibulaire.

This article provides a proposal for the selection and delineation of clinical target volumes for the treatment with radiation of submandibular glands tumours. This article does not deal with external radiotherapy indications but specifies the volumes to be treated if radiotherapy is chosen. High-risk and low-risk peritumoral clinical target volumes are described based on the probability of local tumoral spread. High-risk and low-risk clinical target volumes are illustrated on CT-scan slices. A proposal for the selection of nodal clinical target volumeis also proposed.

Nodal failure patterns and utility of elective nodal irradiation in submandibular gland carcinoma treated with postoperative radiotherapy - a multicenter experience.

BACKGROUND: The patterns of nodal relapse in submandibular gland carcinoma (SMGC) patients treated with postoperative radiotherapy (PORT) remain unclear. This study aims to investigate the nodal failure patterns and the utility of elective nodal irradiation (ENI) in SMGC patients undergoing PORT. METHODS: We retrospectively enrolled 65 SMGC patients who underwent PORT between 2000 and 2014. The nodal failure sites in relation to irradiation fields and pathological parameters were analyzed. ENI regions were categorized into three bilateral echelons (first, levels I-II; second, level III; and third, levels IV-V). Extended ENI was defined as coverage of at least the immediately adjacent uninvolved echelons bilaterally; otherwise, limited ENI was administered. RESULTS: Thirty patients (46%) were stage III-IV, and 18 (28%) were pN+. Neck irradiation included limited (72%) and extended ENI (28%). With a median follow-up of 79 months, 11 patients (17%) developed nodal failures (ipsilateral, N = 6; contralateral, N = 7), 7 (64%) of whom relapsed in the adjacent uninvolved echelons. We identified pN+ (P = 0.030), extranodal extension (ENE, P = 0.002), pT3-4 (P = 0.021), and lymphovascular invasion (LVI, P = 0.004) as significant predictors of contralateral neck recurrence. Extended ENI significantly improved regional control (RC) in patients with pN+ (P = 0.003), ENE (P = 0.022), pT3-4 (P = 0.044), and LVI (P = 0.014), and improved disease-free survival (DFS) in patients with pN+ (P = 0.034). For patients with ≥2 coincident adverse factors, extended ENI significantly increased RC (P < 0.001), distant metastasis-free survival (P = 0.019), and DFS (P = 0.007); conversely, no nodal recurrence was observed in patients without these adverse factors, even when only the involved echelon was irradiated. CONCLUSIONS: Nodal failure is not uncommon in SMGC patients treated with PORT if pN+, ENE, pT3-4, and LVI are present. Extended ENI should be considered, particularly in patients with multiple pathological adverse factors.

Neutron Beam Radiation Therapy: An Overview of Treatment and Oral Complications When Treating Salivary Gland Malignancies.

PURPOSE: There is limited information in the literature regarding the oral complications of neutron radiotherapy, with an associated lack of guidelines for their management. The purpose of this study was to review the indications, dosing, prognosis, and oral complications of neutron radiotherapy for salivary gland malignancies. MATERIALS AND METHODS: This is a retrospective case series of patients with salivary gland malignancies treated with neutron radiotherapy by the Radiation Oncology Department at the University of Washington from 1997 to 2006. Variables included patient demographics, tumor staging and characteristics, operative treatment, final diagnosis, operative and pathologic findings (ie, perineural invasion, lymph node involvement, and skull base invasion), dosing, complications, and locoregional control and survival rates. Data were extracted from patients' charts and by telephone for follow-up and quality-of-life information. RESULTS: The sample was composed of 140 patients (49% men, 51% women) with a mean age of 53 years (standard deviation, 15 yr). Adenoid cystic carcinoma of the submandibular gland was the most common tumor type and location. Post-treatment trismus occurred in 56%. Acute mucositis and xerostomia occurred in approximately 88 and 89% of patients, respectively. Osteoradionecrosis was reported in 5.7% of patients. The 6-year survival rate was 58% and the 6-year locoregional control was 72%. The current standard neutron dose for head and neck tumors is 1.15 neutron Gray (nGy) 4 times per week for 4 weeks (total, 18.4 nGy), which is an equivalent amount of radiation as the standard 60 to 70 Gy given for 6 to 7 weeks with conventional photon radiation. CONCLUSION: The 6-year overall survival of 58% found in this study compares favorably to the survival rate reported in the literature for traditional photon radiation treatment of advanced salivary gland tumors. The dental profession should be educated regarding neutron radiotherapy and its indications, dosing methods, and oral complications.

Comparative study of dose distributions and cell survival fractions for 1H, 4He, 12C and 16O beams using Geant4 and Microdosimetric Kinetic model.

Depth and radial dose profiles for therapeutic (1)H, (4)He, (12)C and (16)O beams are calculated using the Geant4-based Monte Carlo model for Heavy-Ion Therapy (MCHIT). (4)He and (16)O ions are presented as alternative options to (1)H and (12)C broadly used for ion-beam cancer therapy. Biological dose profiles and survival fractions of cells are estimated using the modified Microdosimetric Kinetic model. Depth distributions of cell survival of healthy tissues, assuming 10% and 50% survival of tumor cells, are calculated for 6 cm SOBPs at two tumor depths and for different tissues radiosensitivities. It is found that the optimal ion choice depends on (i) depth of the tumor, (ii) dose levels and (iii) the contrast of radiosensitivities of tumor and surrounding healthy tissues. Our results indicate that (12)C and (16)O ions are more appropriate to spare healthy tissues in the case of a more radioresistant tumor at moderate depths. On the other hand, a sensitive tumor surrounded by more resistant tissues can be better treated with (1)H and (4)He ions. In general, (4)He beam is found to be a good candidate for therapy. It better spares healthy tissues in all considered cases compared to (1)H. Besides, the dose conformation is improved for deep-seated tumors compared to (1)H, and the damage to surrounding healthy tissues is reduced compared to heavier ions due to the lower impact of nuclear fragmentation. No definite advantages of (16)O with respect to (12)C ions are found in this study.

Management of sarcomatoid salivary duct carcinoma of the submandibular gland duct with coexisting seropositive human immunodeficiency virus.

BACKGROUND: Sarcomatoid salivary duct carcinoma of the submandibular gland is extremely rare. This paper highlights the impact of surgery and adjuvant radiation therapy on the outcome of this disease. METHODS: A 59-year-old man with human immunodeficiency virus presented with a painless, rapidly growing left neck mass. Biopsy followed by surgical excision of the left submandibular gland revealed sarcomatoid salivary duct carcinoma of the submandibular gland duct with perineural invasion and close margins, for which he underwent adjuvant radiotherapy. Post-operative positron emission tomography and computed tomography revealed no residual or metastatic disease. Pathological analysis of tumour-node-metastasis staging revealed a T2 N0 M0 (stage II) tumour. RESULTS: The patient tolerated his treatment without serious acute or long-term side effects. There was no evidence of disease on comprehensive examination or on positron emission tomography or computed tomography scans at the 4.6-year follow up. CONCLUSION: Surgery followed by adjuvant radiotherapy provided practical locoregional control with acceptable toxicity. Further detailed case reports are warranted to optimise the management of this rare malignancy.

Results in the management of malignant submandibular tumours and guidelines for elective neck treatment.

BACKGROUND: Malignant submandibular gland tumours are rare tumours treated primarily with surgery. PURPOSE: This retrospective study was done to determine the effectiveness of adjuvant radiation therapy (RT), to document the patterns of failure, and to define the prognostic variables for treatment outcome. MATERIALS AND METHODS: Between 1960 and 2002, 74 patients diagnosed as having malignant submandibular gland tumours were treated with radical surgery. The surgery included neck dissection in 37 patients and adjuvant RT in 50 patients with high-risk features. RESULTS: Forty-one (54%) patients experienced disease relapse. The local recurrence rates were 35% in those treated only with surgery and 21% in patients who underwent postoperative RT (p  =  .20). The risk of subclinical nodal metastases in the clinical N0 neck was 21%. CONCLUSIONS: The American Joint Committee on Cancer stage approached statistical significance for cause-specific survival. Although not statistically significant, RT probably reduced local recurrence. All patients with malignant submandibular tumours except T1 need elective neck treatment.

[A case of submandibular gland cancer in elderly patients showed significant effect by S-1 and intravenous docetaxel chemotherapy concurrent with radiotherapy].

An elderly case of with advanced head and neck cancer treated by intravenous infusion chemotherapy with weekly docetaxel( DOC)and concurrent radiotherapy was reported. The patient was a 77-year-old man. Clinical diagnosis was submandibular gland carcinoma. He was treated by intravenous infusion chemotherapy with weekly DOC and concurrent radiotherapy (total dose 66 Gy). Two months after irradiation, PET-CT showed a partial response (PR). Therefore, chemotherapy of S-1 (80 mg/day) for 2 weeks every 3 weeks was performed. Two months after the end of chemotherapy, PET-CT showed a complete response(CR). This therapy is effective for the treatment of advanced head and neck cancers for elderly inoperable patients.

Prognostic factors and outcome analysis of submandibular gland cancer: a clinical audit.

PURPOSE: To retrospectively review a long-term, single-institution experience of subjects with submandibular gland malignancies treated with definitive locoregional therapy with an aim to identify clinicopathologic variables that correlate with outcomes. MATERIALS AND METHODS: A comprehensive chart review of 47 patients presenting to the institute from 1993 to 2005 with a histologic diagnosis of submandibular salivary gland cancer was performed to extract demographic data, clinicopathological characteristics, and treatment details. Clinical and pathologic factors were correlated with locoregional control, distant metastases free survival, and disease-free survival using log-rank test and Cox proportional hazards model for univariate and multivariate analysis, respectively. RESULTS: With a median follow-up of 29 months (interquartile range, 13 to 64 months), the actuarial 5-year locoregional control, distant metastasis-free survival, and disease-free survivals of the entire cohort were 80.5%, 86.1%, and 71.8%, respectively. Overall stage grouping (P = .008), perineural invasion (P = .04), and radiotherapy dose (P = .033) were significant predictors of locoregional control. Overall stage grouping (P = .014) and T stage (P = .05) also affected disease-free survival. Extraglandular involvement showed a trend toward poorer outcome. CONCLUSIONS: Submandibular gland cancer is a rare disease with histologic diversity and variable clinical behavior. Overall stage grouping and perineural invasion remain the most significant predictors of outcome. Adequate doses of adjuvant radiotherapy improve locoregional control in high-risk patients.

Carcinomas arising in the submandibular gland: high propensity for systemic failure.

BACKGROUND: Cancers of the submandibular gland are uncommon and only a few small series have reported patient survival and prognosis. METHODS: We examined the treatment outcomes of 62 patients with surgically treated submandibular gland carcinomas. All patients underwent surgical excision with/without neck dissection, and 41 received postoperative radiotherapy for high-grade, invasive, positive margin, or regionally metastatic tumors. The locoregional control and survival rates were calculated by the Kaplan-Meier method and prognostic factors were calculated from uni- and multivariate analyses. RESULTS: Of the 62 submandibular gland carcinomas, 19 were adenoid cystic, 11 were mucoepidermoid, and 10 were salivary duct carcinomas, and 8 were carcinomas in pleomorphic adenoma. Actuarial 5-year locoregional control, distant metastasis-free survival, disease-free and overall survival rates were 69.7%, 65.8%, 52.8%, and 56.8%, respectively. In multivariate analysis, T category and histological grading were prognostic for disease-free survival (P < 0.01), and T category and resection margins were prognostic for locoregional control (P < 0.02). Distant metastases were found in 21 patients (33.9%) at initial staging (n = 2) or follow-up (n = 19). CONCLUSIONS: Despite effective locoregional treatment, approximately one-third of patients with submandibular gland carcinomas may fail systemically, resulting in poor survival. New, more effective therapies may be required for these patients.

[Epithelial-myoepithelial carcinoma of the submandibular gland: a case report]. / Submandibuler bezde epitelyal-miyoepitelyal karsinom: Olgu sunumu.

Epithelial-myoepithelial carcinomas are rare, low-grade, malignant salivary gland tumors. They are mostly seen in the parotid gland. The submandibular gland is a rare localization. A 54-year-old woman presented with a painless lump on the left side of the neck. Examination showed a mass with smooth surface in the left submandibular region. Fine needle aspiration cytology of the mass was reported as malignant epithelial tumor metastasis. Computed tomography of the neck showed left submandibular gland hypertrophy. Left submandibular gland excision with functional neck dissection was performed. The histopathological diagnosis was epithelial-myoepithelial carcinoma of the submandibular gland with one lymph node metastasis.

Pleomorphic adenoma of the submandibular gland: an evolving change in practice following review of a personal case series.

We reviewed patients with submandibular gland pleomorphic adenoma treated at a tertiary referral centre in the United Kingdom (1988-2004). Thirty-seven patients were identified, 32 newly diagnosed cases and 5 cases of recurrent disease previously treated elsewhere. The exact pre-operative diagnosis was "unknown" in 76% of the new cases. All cases were surgically excised (41% with extracapsular gland excision and 59% by selective level Ib, IIa and III neck dissection). Temporary marginal mandibular nerve neuropraxia was documented in 25% of cases. All 32 new cases remain clinically tumour free at the time of writing. In patients with recurrent disease, complete microscopic tumour clearance was achieved in three of the five cases, however all remain clinically tumour free. Pleomorphic adenomas of the submandibular gland are uncommon, with good prognosis following complete tumour excision. Recurrent tumours, however, are frequently multi-focal and difficult to excise completely. The adequacy of primary surgery is crucial and supports an approach for a more radical excision primarily by a selective level lb, IIa and III neck dissection; ensuring complete disease clearance for pleomorphic adenoma, avoiding the risks of tumour spillage associated with a limited excision and tumour handling; and removing the primary echelon of lymph nodes at risk of metastasis if the pathology turns out to be malignant.

Effect of initial treatment on disease outcome for patients with submandibular gland carcinoma.

OBJECTIVE: To elucidate the effect on outcome of initial surgical enucleation with or without definitive surgical resection and radiation therapy for patients with submandibular gland carcinoma. DESIGN: Retrospective clinicopathological review. SETTING: Tertiary referral center. PATIENTS: Eighty-seven consecutive patients (mean follow-up, 8.7 years) with primary submandibular gland carcinoma. MAIN OUTCOME MEASURES: Review of proven cases of primary carcinomas of the submandibular gland treated at our institution during a 33-year period to determine the effect of the type of biopsy and subsequent treatment on locoregional disease control, disease-specific survival, and overall survival. RESULTS: There was no statistically significant difference in locoregional disease control, disease-specific survival, or overall survival between patients undergoing enucleation of the gland vs patients undergoing enucleation of the gland followed by definitive surgical resection before any radiation therapy. There were no locoregional recurrences among 28 patients treated with enucleation and radiation therapy, compared with 3 locoregional recurrences (7%) among 42 patients treated with enucleation followed by definitive surgical resection before any radiation therapy. Twenty-nine (69%) of 42 patients undergoing a second surgical procedure had evidence of residual carcinoma in the final surgical specimen. CONCLUSIONS: En bloc surgical resection followed by radiation therapy remains the standard treatment for patients with submandibular gland carcinoma. Patients without clinical and radiographic evidence of disease after enucleation may be adequately treated with subsequent radiation therapy. Definitive surgical resection remains the treatment of choice for patients with clinical or radiographic evidence of disease after enucleation of the gland.

Carcinosarcoma ex recurrent pleomorphic adenoma of the submandibular gland.

We report a case of carcinosarcoma ex recurrent pleomorphic adenoma in the submandibular region of a 56-year-old Japanese man. He presented with a 2-year history of a rapidly growing mass in the submandibular region. He reported undergoing excision of a nodule in the same region 10 years earlier. Incisional biopsy confirmed the diagnosis of pleomorphic adenoma. The lesion was excised surgically. The resected tumor measured 40 x 20 mm and was composed of two large nodules and multiple small satellite nodules in the subcutaneous tissue. Histopathologically, one large nodule was carcinosarcoma while the other large nodules and small satellite nodules were pleomorphic adenoma. The former large nodule showed a variegated pattern with carcinomatous components (poorly differentiated adenocarcinoma, salivary duct carcinoma, squamous cell carcinoma and undifferentiated carcinoma) and sarcomatous components (spindle cell sarcoma, chondrosarcoma, liposarcoma and rhabdomyosarcoma). Based on the clinical history and histopathology, we consider the lesion to have originated from recurrent pleomorphic adenoma.

A case of carcinosarcoma arising in the submandibular gland.

A 54-year-old man presented with an 8-year history of a hard asymptomatic mass of the left submandibular area. Total excision of the left submandibular gland with radical neck dissection was performed under a diagnosis of a submandibular tumor, probably a malignant mixed tumor. The pathologic diagnosis was carcinosarcoma consisting of carcinomatous and sarcomatous elements. The epithelial component was composed of squamous cell carcinoma, undifferentiated carcinoma, and adenocarcinoma. The nonepithelial component was composed of chondrosarcoma, osteosarcoma, spindle cell sarcoma, rhabdomyosarcoma, and liposarcoma. In the central area of the tumor, a few remnants of benign pleomorphic adenoma were identifiable. The finding suggested that in our patient, the carcinosarcoma arose from a preexisting pleomorphic adenoma. In view of the expected aggressive nature of the tumor, the patient was treated with postoperative radiotherapy of 60 Gy total, in 30 daily fractions of 2 Gy, and chemotherapy. He currently remains well and free of disease 24 months after treatment.

A case of squamous cell carcinoma of the head and neck producing granulocyte-colony stimulating factor with marked leukocytosis.

In squamous cell carcinoma of the head and neck (SCCHN), tumor cells have been shown to secrete detectable amounts of various cytokines, such as interleukin (IL)-6, IL-10, and transforming growth factor (TGF)-beta. These tumor-derived factors might be responsible for promoting malignancy. Here, we describe a SCCHN patient with tumor produced G-CSF and characterized by marked leukocytosis. In this 45-year-old man, severe leukocytosis developed in parallel with aggressive tumor growth. G-CSF production by the tumor was confirmed by immunohistochemistry (IHC). Serum G-CSF levels were elevated. The leukocyte counts and the blood G-CSF level decreased following a course of radiotherapy. Tumor cells were also positive for G-CSF receptor, suggesting autocrine growth regulation by G-CSF. Moreover, the tumor cells were also investigated by IHC with anti-p53, anti-P-glycoprotein (P-gp), anti-thymidylate synthase (TS), and anti-dihydropyrimidine dehydrogenase (DPD), which molecules are thought to contribute the acquisition of therapeutic resistance. The tumor cells were positively stained for TS and DPD, but neither p53 nor P-gp. These results suggest that a variety of molecules may be responsible for acquisition of high malignancy.

Epithelial-myoepithelial carcinoma of the submandibular gland with symptomatic lung metastases treated with chemotherapy.

This report concerns a patient with symptomatic lung metastases from an epithelial-myoepithelial carcinoma of the submandibular gland. Although the efficacy of chemotherapy is unknown in this disease, our patient was treated with cisplatin combined with 5-fluorouracil and later with paclitaxel and cyclophosphamide. Chemotherapy allowed disease stabilization and relief of the pulmonary symptoms. This is the first report on the use of chemotherapy in this very rare salivary gland carcinoma.

First clinical case of boron neutron capture therapy for head and neck malignancies using 18F-BPA PET.

BACKGROUND: We investigated the application of boron neutron capture therapy (BNCT) to suitable cancers other than glioblastoma and melanoma. Head and neck malignancies were consequently selected as adaptable cancers. We reported the clinical results of our first case treated and discussed several advantages to the application of BNCT to head and neck tumors. METHODS: The patient was a 48-year-old woman with recurrent submandibular gland cancer. We confirmed the p-boronophenylalanine (BPA)-accumulating capacity of the tumor by fluorine-18-labeled p-boronophenylalanine positron emission tomography ((18)F-BPA PET) before BNCT. The tumor/normal tissue boron concentration ratio was 2.9. The patient underwent a preirradiation CT scan for treatment planning performed using the "SERA" software program. The tumor was irradiated at the Kyoto University Research Reactor with epithermal neutrons 5 MW for 90 minutes. The tumor dose and normal tissue dose calculated ranged from 20.0 to 25.2 Gy and from 3.2 to 5.8 Gy, respectively. RESULTS: To date there has been continuous complete regression in the tumor and no acute and chronic complications for 1.5 years. CONCLUSIONS: Although only 1 patient has shown complete regression and additional long-term follow-up should be required to assess this treatment, we believe that head and neck tumors are suitable for BNCT and that such excellent results will have a great impact on patients in the near future.

A case of hypothyroid Graves' disease following external radiation therapy to the cervical region.

A case of hypothyroid Graves' disease occurred following external radiation therapy to the cervical region is described. Severe hypothyroidism developed in a 56-year-old man 6 months after external radiation therapy for submandibular cancer. Serological evaluation of thyroid autoimmunity revealed the presence of antithyroid antibodies and thyrotropin-binding inhibitory immunogloblins (TBII). Diplopia, limitation of downward gaze, and palpebral edema developed 2 years after levothyroxine replacement therapy. Ocular magnetic resonance imaging revealed marked hypertrophy of the bilateral extraocular muscles with signal hyperintensity on T2-weighted images. This infiltrative ophthalmopathy showed marked improvement after additional treatment with high-dose methylprednisolone and orbital radiation, in parallel with a decrease in TBII. These results suggest that radiation-associated thyroidal injury might be associated with the etiology of hypothyroid Graves' disease.