Treatment Of Adenoid Cystic Carcinoma Research Articles

An apparent radiation-induced carcinoma of the parotid gland following treatment for adenoid cystic carcinoma of the sublingual gland: A case report

A p w l a o t is well known that radiation to the head and neck egion can predispose to increased risk for malignant ransformation of many tissues, including salivary lands.1-3 In irradiated patients, malignant transformaion risk is higher (13to 40-fold) than it is for that of aturally occurring malignancies, with a latency peiod ranging from 6 to 32 years.4 Because of this risk, adiotherapy for benign head and neck lesions such as ervical tuberculous lymphadenitis, goiter, ear tube bstruction, and others is limited.5,6 However, radioherapy for head and neck cancers is an effective djunct to surgical treatment. Technical improveents in radiotherapy for cancer have produced a arge population of long-term survivors clinically free f disease. Therefore, some long-term survivors may evelop a second malignant tumor following radioherapy for their first cancer. The incidence of radiaion-induced cancer following radiation therapy is es-

Imatinib mesylate as treatment for adenoid cystic carcinoma of the salivary glands: Report of two successfully treated cases

Adenoid cystic carcinoma (ACC) is a malignant neoplasia of the salivary glands that is treated primarily by surgery. Local control and survival are usually compromised despite surgery. Expression of KIT tyrosine kinase is involved in the pathogenesis of ACC. Imatinib mesylate is a potent inhibitor of KIT tyrosine kinase, so we explored the possibility that ACC could be a potential target for this drug. We report two cases of unresectable ACC treated with imatinib mesylate in the context of recurrent disease (case 1) and locally advanced tumor at its initial presentation (case 2). Both patients responded well to treatment with imatinib mesylate. Significant regression of recurrent disease (case 1) resulted in a successful salvage surgical resection; the locally advanced tumor (case 2) had an excellent response to treatment, but, unfortunately, the patient refused salvage resection. This is the first time ACC is reported to respond to imatinib mesylate. Studies in which more patients are enrolled in controlled clinical trials are needed to confirm this observation.

Establishment and characterization of metastasizing cell lines from a heterotransplanted human adenoid cystic carcinoma

Adenoid cystic carcinoma (ACC) is a rare malignant tumor of the head and neck occurring in the salivary glands. We established a human ACC line which is serially transplantable in nude mice and designated it as KOA-1. The KOA-1 tumor doubled in 9.3 days and retained the histologic characteristics of a solid pattern of ACC even after 22 serial passages. The KOA-1 metastasized to the lung 2 months after subcutaneous transplantation into nude mice. We further established a subline of KOA-1 by an in vivo selection method and named it KOA-1L3. The KOA-1L3 doubled in 1.3 days and metastasized to the lung within 1 week after subcutaneous transplantation. These tumor lines may serve as a useful model for exploration of the biological behavior and treatment of human ACC.

Adenoid cystic carcinoma in the head and neck: An updated survival analysis

Objectives: The study of adenoid cystic carcinoma (ACC) of the salivary gland requires long-term follow up due to the slow growth rate of the tumor and its propensity to recur many years after therapy. Current management strategy for ACC has varied little in the last 60 years, but techniques in surgical and radiotherapy have improved. We have retrospectively studied patients with adenoid cystic carcinoma of the salivary gland during the last 25 years to determine current survival data at our institution. Methods: Forty-two patients treated for ACC of the salivary gland between 1975 and 2003 were registered at Northwestern Memorial Hospital. Kaplan-Meier analysis was used to characterize survival for this patient population. Tumor site, staging, and size of tumor were analyzed to determine their relationship to patient survival. Prognostic factors were compared to determine if each played a significant role in predicting mortality. Results: Of the 42 patients studied, 19 patients died during follow-up after receiving treatment for ACC. Twenty-three patients were alive at the date of last contact. Kaplan-Meier analysis of the 42 patients yielded a 5-year survival rate of 82.5% and a 10-year survival rate of 61%. Tumor site, stage, and size appeared to influence survival. Conclusion: Our review represents the most current assessment of survival for patients with adenoid cystic carcinoma at our institution. The data presented in our study concur with more recent literature, suggesting survival probability in patients with adenoid cystic carcinoma may be higher due to improved surgical technique and management with radiation therapy.

Adenoid cystic carcinoma of the head and neck: a review.

This purpose of this article is to review and provide an update of current publications on the evaluation and management of adenoid cystic carcinoma. Adenoid cystic carcinoma is an uncommon salivary gland malignancy that presents insidiously and is generally advanced when diagnosed. Current effective treatment modalities include surgery and irradiation, but locoregional recurrences are frequent and may present as early as 2 years. Patients survive with recurrent and metastatic disease for several years despite not being offered any treatment. Molecular analysis of the tumors is being undertaken, with optimistic results capable of selecting high-risk patients who may benefit from adjuvant treatment such as chemotherapy Little progress has been made in advancing "curative" treatment of adenoid cystic carcinoma of the head and neck. The disease is said to have a fatal outcome. The time is now opportune for a multicenter, randomized, controlled trial to identify patients who would benefit from adjuvant radiotherapy and/or chemotherapy in the control of locoregional recurrences and the prevention of distant metastases.

Adenoid cystic carcinoma of the head and neck—a 20 years experience

In this retrospective study we give a clinical review of our experience with adenoid cystic carcinoma (ACC) and compare our results with those reported in the literature. Between 1981 and 2000, 74 patients with this disease were treated at our department. Complete resection was reached in 45 cases. Fourteen patients received postoperative radiation. Local control rates at 5, 10 and 15 years were 64%, 56% and 52% with a mean local control time of 11.1 years. Tumour size (P≤ 0.001), perineural invasion (P≤ 0.001) and margin status (P≤ 0.001) showed significant influence on local control. Statistically, we were not able to demonstrate a positive effect for postoperative radiation. Distant control rates at 5, 10 and 15 years were 72%, 62% and 59% with a mean distant control time of 14.4 years. Distant failure was diagnosed in lungs and bones and occurred independently of local treatment outcome. Overall survival rates at 5, 10 and 15 years were 71%, 54% and 37% with a mean overall survival of 11.2 years. Recurrence-free survival rates at 5, 10 and 15 years were 57%, 45% and 37% with a mean recurrence-free survival of 9.1 years. The survival rates at 5, 10 and 15 years after diagnosis of tumour progression were 35%, 15% and 0% with a mean survival time of 4.7 years. Our results provide insights to the unusual nature of ACC, which may be useful for making clinical decisions. However, prospective randomized multicentric studies are needed to define the optimal treatment for ACC with special regard to adjuvant treatment modalities.

The biological behaviour of human adenoid cystic carcinoma cells transduced with interleukin-2-gene

Adenoid cystic carcinoma (ACC) of the salivary glands is a highly infiltrative malignant tumour with a tendency for lung metastasis. Gene therapy could be a potentially effective therapy for ACC and its metastasis. The aims of the study were: To transduce interleukin-2 (IL-2) gene into an ACC cell line with predisposition for lung metastasis (ACC-M); to compare the bioactivity of the gene-transduced cells and the parent cell line in vitro and in vivo.The IL-2 gene was transduced via a bicistronic retroviral vector into the ACC-M cells. The growth rate and DNA cell cycles of the parent ACC-M, the control viral vector AmGCEN, and the gene transduced AmIL-2 cell cultures were compared quantitatively and by flow cytometry, respectively. The tumourigenic ability of the three cell lines was verified by inoculation in athymic nude mice. The tumours developed were extracted and compared quantitatively and histologically.There was no difference in the growth rate and the DNA count between the ACC-M, AmGCEN, and AmIL-2 cell cultures. In the animal experiment, both the ACC-M and AmGCEN cells stimulated lung metastasis in all the mice, whereas there was no tumour found in the 1×106 AmIL-2 cells inoculation. On 3×106 AmIL-2 cells stimulation, three out of six mice developed tumours but the mass and volume of the tumours were smaller than the other two groups. Under light microscopy, the ACC-M tumours were mainly poorly differentiated with minimal cellular matrix, whereas the AmIL-2 tumours were well differentiated with ample matrix.The transduction of IL-2 gene can reduce the tumourigenicity of ACC-M cells and induces tumour cell differentiation in mice. The IL-2 gene can be a potential effective gene for the treatment of adenoid cystic carcinoma of salivary glands and its lung metastasis.

Adenoid cystic carcinoma of the base of the tongue.

A retrospective review of 14 patients with adenoid cystic carcinoma of the tongue treated between 1955 and 1997 was performed. Treatment consisted of surgery (n = 2), radiotherapy (n = 2), chemotherapy (n = 1), or combination therapy (n = 9). The 2-, 5-, and 10-year absolute survival rates were 92%, 79%, and 63%, respectively. Seventy-five percent of the patients who died of cancer succumbed to distant metastases. However, long-term survival was common despite a high incidence of local and distant recurrence. The presence of positive surgical margins, the incidence of regional metastases, the incidence of perineural invasion, the initial stage of disease, and the eventual development of locoregional recurrence and distant metastases did not significantly alter the survival rate. Surgical extirpation combined with postoperative radiotherapy is advocated for the treatment of adenoid cystic carcinoma of the tongue. Given the indolent nature of this disease process, surgery should be directed toward conservation of speech and swallowing function.

Combined treatment of adenoid cystic carcinoma of the salivary glands

A retrospective review of the experience of a single surgeon over a 20-year period is presented. Fifteen patients with primary adenoid cystic carcinoma of the major (6) or minor (9) salivary glands underwent combined treatment with wide local excision and radical postoperative radiotherapy. The actuarial survival is 100% at 5 years and 62% at 10 and 15 years. The disease-specific survival is 100% at 5 years and 86% at 10 and 15 years. There were no loco-regional recurrences. Wide local excision and radical postoperative radiotherapy seems to be an effective treatment for adenoid cystic carcinoma of the salivary glands.

Combined treatment of adenoid cystic carcinoma of the salivary glands

A retrospective review of the experience of a single surgeon over a 20-year period is presented. Fifteen patients with primary adenoid cystic carcinoma of the major (6) or minor (9) salivary glands underwent combined treatment with wide local excision and radical postoperative radiotherapy. The actuarial survival is 100% at 5 years and 62% at 10 and 15 years. The disease-specific survival is 100% at 5 years and 86% at 10 and 15 years. There were no loco-regional recurrences. Wide local excision and radical postoperative radiotherapy seems to be an effective treatment for adenoid cystic carcinoma of the salivary glands.

The role of skull base surgery for the treatment of adenoid cystic carcinoma of the sinonasal tract.

Adenoid cystic carcinoma (ACC) of the sinonasal tract is an aggressive malignancy associated with a poor 5-year survival rate. The role of skull base surgery for the treatment of patients presenting with sinonasal ACC and its impact upon their survival has not previously been evaluated. A retrospective review of 35 patients with ACC of the sinonasal tract who were treated with surgery and radiation therapy at the University of Pittsburgh Medical Center was performed to evaluate patient outcome. Local recurrence of tumor following surgery and radiation therapy was observed in 36% of the patients originally treated at the University of Pittsburgh Medical Center. Fourteen percent of these patients developed a regional tumor recurrence, and 21% developed distant metastases. We did not identify any tumor-related factors that predicted patient outcome. Local recurrences were treated with salvage surgical excision, and, despite aggressive management, only 1 of 17 patients with local recurrence was considered cured (NED) at 24 months (follow-up after salvage surgery). Overall, disease-free survival was 46.4%, at a median follow-up of 40 months. ACC of the sinonasal tract is an aggressive malignancy. Skull base surgery has facilitated the gross total excision of advanced lesions that were deemed inoperable in the past, but has not resulted in an overall improvement in disease-free survival. Local recurrence portends a very poor prognosis, despite aggressive salvage regimens. Alternative therapies for local recurrences warrant further investigation. Prospective, randomized studies are necessary to evaluate the outcome of patients treated with aggressive multimodal treatment regimens, including chemotherapeutic regimens.

Combined modality treatment of adenoid cystic carcinoma of the salivary glands

Combined modality treatment of adenoid cystic carcinoma of the salivary glands

Analysis of Factors Affecting Long-Term Treatment Results of Adenoid Cystic Carcinoma of the Nose and Paranasal Sinuses

At Akita University Hospital (from 1971 to 1987) and at Chiba University Hospital (from 1983 to 1988), 17 patients with adenoid cystic carcinoma of the nose and paranasal sinuses were treated by en bloc tumor resection followed by primary reconstruction of the maxilla. Pre- and post-operative radiation was combined in 5 and 6 patients, respectively. Ten-year cancer-free survival rates were 59.3% in the 12 patients with maxillary sinus tumors and 50% in the 4 patients with nasal tumors. One patient with a sphenoid sinus tumor died within 5 years. Ten-year cancer-free survival was affected markedly by grade of tumor extension. Among T1NOMO and T2NOMO patients (of which there were 1 and 7, respectively), only 1 died of unrelated causes, and 6 patients survived cancer-free for more than 10 years. However, 4 of the 6 T3NOMO patients died, and the cause of death was distant metastasis in 2, intracranial tumor extension in 1, and unrelated causes in 1. All 3 T4NOMO patients died, 2 due to intracranial tumor extension and 1 of unrelated causes. The cause of death was distant metastasis in 3, local recurrence in 3, 2 of whom had intracranial tumor extension, and unrelated causes in 2. Prevention of distant metastasis and intracranial tumor extension was considered to be crucial for improving treatment results after en bloc tumor resection. Preoperative radiation was thought to decrease incidence of distant metastasis. In 5 patients who had preoperative radiation, 4 survived cancer-free for more than 10 years, and only 1 patient died of unrelated cause. However, of the 6 patients who had postoperative radiation, 2 died of distant metastasis and another 2 died of intracranial tumor extension. Of the 6 patients who did not have radiation therapy, the causes of death were local recurrence in 1, distant metastasis in 1 and unrelated causes in 1. Preoperative radiation in 5 patients showed histopathologically moderate or marked degeneration and necrosis of tumors in all patients. Although the number of patients in this study is too small to allow statistical analysis of the data, our present modality of treatment for adenoid cystic carcinoma of the nose and paranasal sinuses is routine combination of preoperative full dose radiation, en bloc tumor resection and primary reconstruction, including en bloc resection of the cranial base in selected T4 patients.

Adenoid cystic carcinoma of the salivary glands: a review of 10 years.

A retrospective analysis was performed of 50 patients with adenoid cystic carcinoma who were seen in the Department of Radiation Oncology, University of Witwatersrand, Johannesburg, South Africa, in the past 10 years. There were 25 men and 25 women with a mean age of 52 years (age range, 21 to 88 years). Five patients had metastatic disease, and 17 had neural invasion. Thirty-four patients had surgery (11, complete; 23, microscopic residual). Sixteen patients had radiotherapy as initial management. The disease-free survival was 26%, overall survival was 29%, and local control was 30% at 10 years. Most recurrences occurred in the first 3 years. Nine patients had metastasis following treatment. The mean survival after metastasis was 15 months. Seven prognostic variables were analyzed using the log-rank test. There was no impact of age, site, type of salivary gland (major vs. minor), tumor stage, node positivity, or neural invasion on disease-free survival, overall survival, or local control. Extent of surgical resection (complete vs. microscopic residual) had a significant impact on disease-free survival and local control (P < 0.05) but no impact on overall survival (P > 0.05) because of the slow-growing nature of these tumors. Similarly, patients who had microscopic residual after surgery and were treated with radiotherapy did better than those who had biopsy and radiotherapy, although this was not significant statistically (P > 0.05). Thus, whenever possible, every attempt must be made to remove all microscopic tumor by surgery. Addition of postoperative radiotherapy with high-energy photons did not improve the locoregional control or survival in our series. There is a place for neutrons in the treatment of adenoid cystic carcinomas in advanced cases of inoperable or recurrent tumors, as a review of literature shows.

THE ROLE OF RADIATION THERAPY IN THE MANAGEMENT OF SALIVARY GLAND NEOPLASMS

SUMMARY The previously widely spread misconception that salivary gland malignancies are radioresistant and that radiation therapy is of only palliative value can no longer hold true. The review of the literature, particularly the last 20 years of experi- ence with the use of radiation therapy as an adjunct to surgery and as a primary modality for inoperable tumors, clearly shows that radioresistance is not an issue. Radiation therapy plays an important role in the management of a large proportion of major and minor salivary gland malignant tumors as well as in certain cases of nonma- lignant tumors (pleomorphic adenoma of the parotid). Adjuvant postoperative radiation therapy is indicated in all high-grade tumors, advanced- stage tumors, positive surgical margins or postoperative tumor residual, positive regional nodes, nerve or perineural involvement, and recurrent tumor. Definitive high LET radiation therapy (fast neutrons) is indicated for unresectable and recurrent tumors and may be the treatment of choice in all cases in which surgery has a low likelihood of achieving negative surgical margins or a high risk of facial nerve damage. Neutron therapy is particularly of benefit in the treatment of adenoid cystic carcinoma.

Neutron radiotherapy for adenoid cystic carcinoma of the head and neck.

Achieving local control in patients with advanced adenoid cystic carcinoma continues to be a therapeutic challenge. From 1984 to 1990, we treated 34 patients with advanced adenoid cystic carcinoma of the head and neck with fast neutron radiation. Patients treated for minimal microscopic disease following surgery were not included in this study. Neutron radiotherapy achieved 5-year actuarial local control and locoregional control rates of 76% and 63%, respectively. Five-year actuarial overall survival and disease-specific survival rates were 65% and 93%, respectively. Eighty-one percent (17/21) of patients treated with neutron therapy alone and 100% (13/13) of the patients treated with neutron therapy and surgery achieved local control. All seven patients with paranasal sinus malignant neoplasms achieved local control. The success achieved in this prognostically unfavorable population affirms the important role of neutron radiotherapy in the treatment of adenoid cystic carcinoma.

Radiotherapy for adenoid cystic carcinoma of the palate.

This is an analysis of 16 patients with adenoid cystic carcinoma of the palate who were treated with curative intent by radiotherapy alone (9) or surgery and radiotherapy (7). No patient received adjuvant chemotherapy. Follow-up ranged from 3 years to 19 years with 69% of the patients having follow-up of more than 5 years. Two patients in the radiotherapy alone group developed local recurrences, and both have had long-term surgical salvage. No local failures were seen in the combined therapy group. Twelve patients (75%) are alive and disease-free. Two patients died with distant disease, one within each treatment group. One patient in the combined therapy group is alive at 8 years with distant metastases, while one in the radiotherapy alone group died of intercurrent disease at 12 years. No significant complications were seen in either treatment group. The role of radiotherapy in the treatment of adenoid cystic carcinoma of the palate is reviewed.

Primary malignant neoplasms of the lacrimal gland.

The clinical characteristics and outcome of 50 primary malignant neoplasms of the lacrimal gland are reviewed: 38 (76%) adenoid cystic carcinomas, six (12%) carcinomas arising in pleomorphic adenoma, and six (12%) adenocarcinomas or other types of carcinoma. Most patients presented with a short history and pain, though pain tended to occur less often and later with adenocarcinoma than with adenoid cystic carcinoma. Pain was unrelated to the duration of symptoms, invasion of bone, loss of trigeminal nerve function, or the frequency and time of tumour recurrence. The estimated disease-free survival for patients with adenoid cystic carcinoma was significantly (p less than 0.01) reduced where half or more of the biopsy specimen showed basaloid differentiation. Eleven patients underwent extended cranio-orbital resection, and the others received a combination of total dacryoadenectomy adenectomy and/or radiotherapy. Survival after adenoid cystic carcinomas appears to be significantly (p less than 0.05) greater when tumour resection is combined with radiotherapy than after radiotherapy alone. At present, however, the rate of disease-free survival after treatment of adenoid cystic carcinoma appears unaltered by cranio-orbital resection, though these latter patients form a relatively greater proportion of those surviving for more than 10 years. Further long-term follow-up is needed to see if this technique does influence survival.

Adenoid cystic carcinoma of the palate.

We reviewed the clinical records of 41 patients who received definitive treatment for adenoid cystic carcinoma arising from the palate. Tumors were divided into three categories depending on local extension and pattern of growth. Surgery, either alone or in combination with post-operative radiation therapy, yielded satisfactory local regional control of the cancer. Patients who had adenoid cystic carcinoma with diffuse microscopic spread into adjacent tissues had the highest propensity for the development of distant metastases.

Adenoid cystic carcinoma: DNA as a prognostic indicator.

A retrospective study was performed on 20 patients with adenoid cystic carcinomas of major salivary glands to see if DNA patterns correlated with their prognoses. Fourteen tumors were found to be DNA diploid; 6 were DNA aneuploid. Histologically, all DNA-aneuploid tumors had solid components, compared with only 5 of the DNA-diploid tumors. All of the DNA-aneuploid tumors recurred, in contrast to only 2 of the DNA-diploid tumors; the difference was highly significant (P less than 0.001). All of the patients with no recurrences had DNA-diploid tumors. In our study, DNA measurements of adenoid cystic carcinomas gave statistically significant information about prognosis and correlated to histological grading. We propose that evaluation of DNA content may be performed before planning the treatment of adenoid cystic carcinomas.