- Pollard JD, Hanasono MM, Mikulec AA, et al (Stanford Univ, Calif)
Head and Neck Cancer in Cardiothoracic Transplant Recipients
Laryngoscope 110: 1257-1261, 2000
Survivors of organ transplantation are at increased risk for cancer (solid malignancies). The rate and behavior of head and neck cancers developing after heart and lung transplantation were analyzed.
1069 cardiaothoracic transplants performed between 1968 and 1998 were followed up for a mean of 9 years. The incidence and natural history of head and neck cancers were analyzed, together with associated risk factors. 120 (11.2%) patients developed nonlymphomatous malignancies.
An aggressive behavior pattern was noted than that of general population. Follow up of transplant patients should be closely monitored for development of malignancy and their aggressive biology should be borne in mind.
According to R. A. Otto 17% transplant patients developed head and neck malignancy. Of these 50% solid malignancies would occur and 1/3rd would be with aggressive behavior.
- Wong RJ, Keel SB, Glynn RJ, et al (Massachusetts Eye and Ear Infirmary, Boston; Massachusetts Gen Hosp, Boston; Harvard Med School, Boston)
Histological Pattern of Mandibular Invasion by Oral Squamous Cell Carcinoma
Laryngoscope 110: 65-72, 2000
Oral squamous cell carcinoma invades the mandible by 2 histologic patterns: (1) an infiltrative pattern (2) an erosive pattern.
Clinical tumor behavior and the patient survival was assessed according to the histological pattern in retrospective study.
68 patients undergoing surgery to include mandibulectomy were studied. The histologic pattern of mandibular invasion was studied. 41 patients had erosive, 23 infiltrative and 4 mixed.
It was concluded that those with infiltrative pattern had worse prognosis as compared with erosive pattern. Infiltrative pattern had aggressive behavior with poorer outcomes including positive surgical margins, recurrence rate, mortality rate, and disease-free interval.
According to R. A. Otto the authors challenge the assumption that mandibular invasion universally portends a poor prognosis. The data still suggests an intrinsic difference between biological behaviors of these invasive patterns, rather than a reflection of bone behavior invasion depth.
- Verellen D, Vanhavere F (Free Univ of Brussels, Belgium; Belgian Nuclear Research Ctr, Mol, Belgium)
Risk Assessment of Radiation-Induced Malignancies Based on Whole-Body Equivalent Dose Estimates for IMRT Treatment in the Head and Neck Region
Radiother Oncol 53: 199-203, 1999
To estimate the risk of radiation-induced malignancies in patients with head and neck cancers, the whole-body equivalent radiation dose was compared between patients undergoing conventional radiation therapy and those undergoing intensity-modulated radiation therapy (IMRT) treatment.
The data suggests that IMRT increased the risk of radiation-induced malignancies by 8 times. Further studies are needed to assess the risk of IMRT.
According to R. A. Otto this indeed could become a limiting factor with IMRT treatment.
- Terris DJ (Stanford Univ, Calif)
Head and Neck Cancer: The Importance of Oxygen
Laryngoscope 110: 697-707, 2000
Background : Oxygen is one of many biological modifiers that contribute to the response of solid tumors to treatment. Polarographic oxygen measurements were obtained from tumors in 63 patients and used in a series of experiments.
Conclusions : The hypoxic regions that exist within cervical lymph node metastases from head and neck cervical carcinoma are distributed randomly. Oxygenation cannot be used as a predictive factor for prognosis, probably because of the multifactorial nature of the biologic behavior of carcinomas of the head and neck.
According to R. A. Otto this is a wonderful article that objectively analyzes the validity of the long-held premise that tumors contain hypoxic centers. The findings have important ramifications for understanding of tumor responsiveness and the reasons behind responsiveness to radiation therapy and chemotherapy.
- Reddding SW, Zellars RC, Kirkpatrick WR, et al (Univ of Texas Health Science Center, San Antonio)
Epidemiology of Oropharyngeal Candida Colonization and Infection in Patients Receiving Radiation for Head and Neck Cancer
J Clin Microbiol 37: 3896-3900, 1999
The effectiveness of fluconazole treatment as determined by antifungal sensitivity was evaluated.
Conclusion : Prophylaxis specific to Candida infection may be appropriate for patients undergoing radiation therapy for head and neck cancers.
- Garewal HS, Katz RV, Meyskens F, et al (Univ of Arizona, Tucson; Univ of Connecticut, Farmington; Univ of California, Irvine; et al)
b-Carotene Produces Sustained Remissions in Patients With Oral Leukoplakia: Results of a Multicenter Prospective Trial
Arch Otolaryngol Head Neck Surg 125: 1305-1310, 1999
Certain nutrients like vitamin E, b-carotene, selenium, and vitamin A are effective in preventing oral cancers. b-Carotene has been shown to cause regression of leukoplakia by previous studies. This study is sought to confirm the effects of b-carotene and the duration of response.
50 patients with measurable leukoplakia lesions were administered b-carotene 30 mg twice daily for 6 months and later randomly to continue for another 12 months and also to receive placebo.
Conclusion : It was found to cause remission and shown to last for at least one year.
According to R. A. Otto, in particular vitamin A and its analogues, vitamin E, b-carotene and selenium have been extensively studied. Vitamin A and its analogues are more effective, however are severely hampered by their toxicity. Patients easily tolerate b-carotene.
Chemopreventive studies of oral leukoplakia continue to be encouraging.
- Wolden SL, Steinherz PG, Kraus DH, et al (Mem Sloan-Kettering Cancer Ctr, New York)
Improved Long-term Survival With Combined Modality Therapy for Pediatric Nasopharynx Cancer
Int J Radiat Oncol Biol Phys 46: 859-864, 2000
A retrospective study was performed on all patients 20 years or younger treated during the period from 1971 to 1998. Patients with distant metastases were excluded. 33 patients with locoregional disease were studied. Radiotherapy alone was used in 13 patients and 20 patients received chemotherapy.
The use of combined therapy improved 10-year disease-free survival rate compared with radiotherapy alone 84% vs 35% and also improved the survival rate compared with radiotherapy alone 78% vs 33%. For severe complications, the 10-year actuarial rate was 24%.
Conclusion : Radiotherapy to the nasopharynx and neck in doses greater than 16 Gy in the presence of gross disease provide excellent local-regional control. The risk of distant metastases is decreased by the addition of chemotherapy, and the survival rate is increased.
- Hughes PJ, Scott PMJ, Kew J, et al (Chinese Univ of Hong Kong)
Dysphagia in Treated Nasopharyngeal Cancer
Head Neck 22: 393-397, 2000
Hong Kong has a high incidence of nasopharyngeal cancer (NDC): 16.4/100,000 as against 1/100,000 elsewhere in the world.
The treatment choice is radiotherapy. Long-term swallowing function was assessed in 50 patients who underwent radiotherapy for NDC.
Conclusion : Xerostomia caused by radiation alone cannot account for a distinctive pattern of swallowing dysfunction, which was noted on videofluoroscopic examination. The findings were consistent with fibrosis or neuromuscular incordination of the pharyngeal constrictors. Laryngeal penetration and aspiration are common findings.
At R. A. Ottos institution 1 case of total esophageal stenosis and several cases of severe esophageal stenosis with combined radiotherapy/chemotherapy were experienced.
Hopefully the incidence of these consequences can be decreased as the treatment is refined and problems are understood.
- Dedivitis RA, de Carvalho MB, Rapoport A (Complexo Hospitalar Heliopolis, Sao Paulo, Brazil)
Transcutaneous Fine Needle Aspiration Biopsy of the Preepiglottic Space
Acta Cytol 44: 158-162, 2000
A study of endoscopically guided transvalecular fine needle aspiration biopsy of this space found a high correlation rate between cytopathologic and histopathologic results.
Therefore transcutaneous needle biopsy of this space was evaluated to stage suproglottic squamaous cell carcinoma. 28 patients were evaluated.
Overall aspiration biopsy were positive in 5 of 6 cases with invasion of the pre-epiglottic space, for sensitivity of 83%, a specificity of 100% and efficiency of 96%.
- Hilgers FJM, van Dam FSAM, Keyzers S, et al (The Netherlands Cancer Inst, Amsterdam; Univ of Amsterdam)
Rehabilitation of Olfaction After Laryngectomy by Means of a Nasal Airflow-Inducing Maneuver: The “Polite Yawning” Technique
Arch Otolaryngol Head Neck Surg 126: 726-732, 2000
Background : Loss of olfactory function complication following laryngectomy patients was noted in almost 2/3rd of patients. This complication has received very little attention. Lack of adequate nasal air-flow by disconnection back upper and lower airways is the cause.
The use of nasal air-flow inducing maneuver (NAIM) to promote olfactory rehabilitation in laryngectomised patient and is discussed.
44 patients were studied. Speech therapist instructed NAIM performance to the patients. NAIM consisted of “polite yawning” with the lips closed, that is, an extending yawning movement performed by lowering the jaw, floor of the mouth, tongue or base of tongue, and soft palate, with the lips severely closed. Digital and manometric strokes were done to study nasal flow. Before and after training the olfactory activity were tested.
Results : Most patients learned the NAIM in a single 30-minute therapy session. Before treatment, 33 patients were nonsmellers. After this 15 had converted to smellers – a success rate of 46%.
According to R. A. Otto by and large speech rehabilitation is talked about but the consequences of loss of olfactory sensation is ignored. It will be worthwhile to see that speech therapies share this knowledge to rehabilitate patients of laryngectomy.
- Singh B, Kim S-H, Carew JF, et al (Mem Sloan-Kettering Cancer Ctr, New York)
Genome-Wide Screening for Radiation Response Factors in Head and Neck Cancer
Laryngoscope 110: 1251-1256, 2000
Introduction : Genetic observations related to radiation response in cell lines derived from head and neck squamous cell carcinomas were examined by comparative genomic hybridization (CGH) for genome-wide screening.
Conclusion : The number of aberrations detected by CGH analysis may be predictive of radiation response. A large trial of primary tumors to verify this relationship and identify specific genetic aberrations related to radiation response.
According to R. A. Otto, again molecular biology surfaces as a recurring theme. To identify chromosomal loci associated with radiation response are needed by genome-wide analytic methods. Traditionally cytogenetic techniques involved have limitations because of cell culture difficulties.
However, keeping this in mind that this is very preliminary data, the potential implications can be considerable, as it can be learnt how to predict-prior to treatment-which tumors are radio responsive and-even more importantly-why?
- Grandis JR, Zeng Q, Drenning SD (Univ of Pittsburgh, Pa)
Epidermal Growth Factor Receptor (EGFR) -Mediated Stat3 Signaling Blocks Apoptosis in Head and Neck Cancer
Laryngoscope 110: 868-874, 2000
Experimental studies after implanting xenografts of SCCHN (squamous cell carcinoma head and neck) tumor cells in nude mice, demonstrated consecutive activation of stat3 plays a significant role in EGFR signaling in SCCHN. This event leads to loss of growth control through antiapopotic mechanism. Stat3 may be useful target for gene therapy for SCCHN.
Much research effort is directed towards understanding of complex signaling pathways involved in regulation of proliferation and apoptosis (cell death) of SCCHN.
Focus is on the transforming growth factor a-EGFR pathway involved in early tumorigenesis of head and neck cancers.
The authors have provided evidence that in vivo liposome-mediated gene therapy with an EGFR antisense plasmid effectively inhibits stat3 activation and that EGFR-mediated stat 3 signaling is critical for SCCHN growth and apoptosis.
- Partridge M, Li S-R, Pateromichelakis S, et al (Kings College Hosp, London)
Detection of Minimal Residual Cancer to Investigate Why Oral Tumors Recur Despite Seemingly Adequate Treatment
Clin Cancer Res 6: 2718-2725, 2000
Various molecular techniques were used to assess the role of minimal residual cancer and genetic mutations in treatment failure for patients with head and neck cancer.
22 consecutive patients with oral cancers were biopsied. 18 patients had clear margins with 36 months follow-up. Molecular studies were performed to detect mutations in tumor distant mucosa and to identify a signature p53 mutation in the primary SCC (squamous cell carcinoma).
6 of 11 patients showed tumor positive surgical margins by molecular studies.
It was concluded that molecular studies and immunocytochemical studies may be useful in identifying patients at risk of locoregional and distant recurrence and thus prognostic implications.
- Lingen MW, Chang K-W, McMurray SJ, et al (Northwestern Univ, Chicago)
Overexpression of p53 in Squamous Cell Carcinoma (SCC) of the Tongue in Young Patients With No Known Risk Factors Is Not Associated With Mutations in Exons 5-9
Head Neck 22: 328-335, 2000
Expression of p53 was studied retrospectively in 21 patients under 40 years. It was overexpressed in all patients but none had mutations in exons 5-9. Therefore molecular mechanisms of SCC in these young patients may vary from the more typical patients.
According to R. A. Otto, it is possible that the mutations occurred in some other exons than 5-9. This suggests different molecular mechanism for SCC patients in young individuals without known risk factor.
- Bockmuhl U, Schluns K, Kuchler I, et al (Humboldt Univ, Berlin)
Genetic Imbalances With Impact on Survival in Head and Neck Cancer Patients
Am J Pathol 157: 369-375, 2000
Histopathogic tumor classification, (in spite of being the method to characterize solid tumors) cannot satisfactorily predict clinical outcome in individual cases. Nodal status is the most useful parameters used in determining the prognosis.
The possibility of genetic imbalances having influence on prognosis was explored. 113 patients were studied by digital image analysis through custom made computer software and genetic imbalances were evaluated.
It was concluded that independent genetic markers provided prognostic information that was more significant than the classic parameters for head and neck cancers. Thus genetic characterization may permit the individualizing of treatment.
According to R. A. Otto, this points to the change required to approach head and neck cancer treatment in future.
- Gleich LL (Univ of Cincinnati, Ohio)
Gene Therapy for Head and Neck Cancer
Laryngoscope 110: 708-726, 2000
Background : Immune system deficits of head and cancer patients include impaired natural killer (NK) activity, T lymphocytes and cytokine production and function. These cancers produce various antigens and provide many target cells. Tumor grows because the immune system fails to respond to tumor-antigens. With use of vectors, gene therapy in vivo places directly into cancer cells new genetic material than can kill these cancer cells but not healthy cells.
This should provide gene needed to the exact area of target cells, express just enough protein for just long enough, produce the correct effect and carry no toxic effects-this perfect vector does not exist as yet. Viral and lipid vectors have been used, each with advantages and disadvantages.
The gene therapy used are “suicide” gene therapy, gene replacement therapy and immunologic gene therapy. These act by replacing or compensating for lost or ineffective tumor suppressor genes, inserting genes that produce cytotoxic substances or modulating the immune system.
This study used alloantigen therapy in 20 patients with advanced head and neck cancer to genetically alter the tumor so that it expressed a class 1 major histocompatibility complex (MHC) to provoke an intense immune response, echoed throughout the tumor.
20 patients who did not express HLA-B7 were treated by use of lipid vector, by direct intratumoral injection of product containing HLA-B7 gene and b2-microglobulin gene, permitting complete expression of 1 MHC antigen.
Patients were assessed for adverse effects, changes in tumor size, time until disease progressed, and survival. Biopsy specimens were tested for various parameters including apoptosis.
Results : No adverse effect was noted. Treated tumors showed evidence of HLA-B7; tumors that responded had increased apoptosis.
Conclusion : Apoptosis was induced and this gene therapy offers a nontoxic treatment.
According to R. A. Otto, this article effectively articulates the current gene therapy strategies, limitations, and potential future directions that clinicians need to be conversant with regarding gene therapy.