Shigeru Sasaki

Mucosa-Adhesive Water-Soluble Polymer Film for Treatment of Acute Radiation-Induced Oral Mucositis

PURPOSEnTo examine the usefulness and safety of a mucosa-adhesive water-soluble polymer film (AD film) containing anesthetics and antibiotics for the treatment of acute radiation-induced oral mucositis.nnnMATERIALS AND METHODSnTo prepare AD films, 600 mg of hydroxy-propyl-cellulose was dissolved in ethyl alcohol, and mixed with a solution containing tetracaine, ofloxacine, miconazole, guaiazulene, and triacetin. The gel obtained was dried to form 30 translucent round sheets (20 mg per sheet) of 7.5 cm in diameter and 0.2 mm in thickness. The AD film showed excellent adhesive and coating properties when placed on wet oral mucosa. From 1993 to 1994, we used the AD film in 25 patients with acute radiation-induced oral mucositis, in an attempt to alleviate their pain and prevent secondary oral infection. All patients had received definitive radiotherapy for oral carcinoma. Intensity and duration of oral pain from mucositis, relief rates at rest and while eating, and presence of bacterial and/or fungal infection were compared with those of 27 patients treated with topical anesthetics (viscous lidocaine, Xylocaine and/or general systemic analgesics from 1990 to 1992 (NonAD Group).nnnRESULTSnThe intensity of oral pain was the same in the two groups. The mean duration of pain of the AD film Group (10 days) was significantly shortened compared with the NonAD Group (15 days). The rates of complete pain relief at rest and while eating of the AD film Group were statistically higher than those of the NonAD Group: 82% vs. 44%, and 68% vs. 22%, respectively. No secondary bacterial or fungal infections were observed in the AD film Group, whereas 4 cases of documented infections were found in the NonAD Group. No acute or chronic adverse effects of AD film were observed during the 3-year follow-up period. The rates for local control of oral carcinoma and overall survival, at the end of the follow-up period, were 96% and 87% for the AD film Group vs. 92% and 85% for the NonAD Group, respectively.nnnCONCLUSIONnThe AD film, containing topical anesthetics and antibiotics, proved useful to alleviate pain due to acute radiation-induced oral mucositis, maintain good peroral feeding, and prevent secondary oral infections, without inducing adverse reactions.

Risk Factors for Severe Dysphagia after Concurrent Chemoradiotherapy for Head and Neck Cancers

OBJECTIVEnThe aim of this study was to investigate the risk factors for dysphagia induced by chemoradiotherapy for head and neck cancers.nnnMETHODSnForty-seven patients with head and neck cancers who underwent definitive chemoradiotherapy from December 1998 to March 2006 were reviewed retrospectively. Median age was 63 years (range, 16-81). The locations of the primary lesion were as follows: larynx in 18 patients, oropharynx in 11, nasopharynx in 7, hypopharynx in 7 and others in 4. Clinical stages were as follows: Stage II in 20 and Stages III-IV in 27. Almost all patients underwent platinum-based concomitant chemoradiotherapy. The median cumulative dose of cisplatin was 100 mg/m(2) (range, 80-300) and median radiation dose was 70 Gy (range, 50-70).nnnRESULTSnSevere dysphagia (Grade 3-4) was observed in 22 patients (47%) as an acute toxic event. One patient required tube feeding even at 12-month follow-up. In univariate analysis, clinical stage (III-IV) (P = 0.017), primary site (oro-hypopharynx) (P = 0.041) and radiation portal size (>11 cm) (P < 0.001) were found to be associated with severe dysphagia. In multivariate analysis, only radiation portal size was found to have a significant relationship with severe dysphagia (P = 0.048).nnnCONCLUSIONSnLarger radiation portal field was associated with severe dysphagia induced by chemoradiotherapy.

Validation of the Total Dysphagia Risk Score (TDRS) as a predictive measure for acute swallowing dysfunction induced by chemoradiotherapy for head and neck cancers

BACKGROUND AND PURPOSEnMethods for predicting acute swallowing dysfunction in patients with head and neck cancers undergoing definitive chemoradiotherapy have not been established. We investigated the validity of the Total Dysphagia Risk Score (TDRS) as a predictive measure for this morbidity.nnnMATERIALS AND METHODSnForty-seven patients with head and neck cancers who underwent definitive chemoradiotherapy between December 1998 and March 2006 were reviewed retrospectively. Median age was 63 years (range, 16-81). Almost all patients underwent platinum-based concomitant chemoradiotherapy. Factors of the TDRS were as follows: T-classification, neck irradiation, weight loss, primary tumour site and treatment modality. Patients were classified into three risk groups according to the TDRS.nnnRESULTSnSwallowing dysfunction was observed in 27 patients (57%) as RTOG grade 2 or higher acute morbidity. This classification was significantly associated with grade 2 or higher acute swallowing dysfunction (P<0.001). In ROC (receiver operator characteristic) analysis, the cut-off value of TDRS was set at 18 (sensitivity=0.81; specificity=0.85). Prediction of severe (grade ≥ 3) acute swallowing dysfunction was similarly obtained.nnnCONCLUSIONnThe TDRS is a useful tool to predict acute swallowing dysfunction induced by chemoradiotherapy for head and neck cancers.

Treatment for non-Hodgkin's lymphoma (stage I, II) of the elderly: Usefulness of local and regional irradiation and reduced dose chemotherapy

PURPOSEnTo examine the usefulness and safety of a new treatment regimen consisting of irradiation to the involved area and adjacent lymph node area, and reduced dose chemotherapy for elderly patients with non-Hodgkins lymphoma.nnnMETHODS AND MATERIALSnThe core of this study was 38 elderly patients older than 65 years old with intermediate or high grade non-Hodgkins lymphoma, and concomitantly suffering from some other geriatric disease. They received involved area irradiation (40 Gy), adjacent lymph node irradiation (30 Gy), and reduced dose chemotherapy (two cycles of 50-70% ACOP: Doxorubicin, Cyclosphosphamide, Vincristine, Prednisone or 70% MACOP-B: Doxorubicin, Cyclophosphamide, Vincristine, Methotrexate, Bleomycin, Prednisone for 4 weeks).nnnRESULTSnThe completion rate of the treatment regimen was 100%. The 5-year local control rate was 98%. The 5-year disease-free survival rate and the 5-year cause-specific survival rate for all patients were 70 and 82%, respectively. No treatment deaths were observed, and the rate of serious complications arising from the treatment was 3%.nnnCONCLUSIONSnThe newly conducted treatment regimen proved to be safe and useful for elderly patients with non-Hodgkins lymphoma concomitantly suffering from some other geriatric disease.

Successful treatment of crizotinib-induced dysgeusia by switching to alectinib in ALK-positive non-small cell lung cancer.

We describe a case of dysgeusia that developed gradually over one week after initiation of crizotinib administration for treatment of ALK-positive non-small cell lung cancer, necessitating discontinuation of the agent. The symptom was accompanied by progressive loss in appetite and body weight. Alectinib, a novel alternative ALK inhibitor, was administered and has been successfully continued without any toxicity, including dysgeusia. The present case indicates that dysgeusia is an important toxicity associated with crizotinib, which could adversely affect nutritional condition and quality of life. We describe the clinical course and present a review of crizotinib-induced dysgeusia.

Two Cases of Thymic Carcinoma Initially Presenting as Bone Metastasis: A Clinical Report and the Usefulness of CD5 Immunohistochemistry for Assessing Bone Lesions.

Thymic carcinoma frequently spreads to the pleural space, regional lymph nodes, liver and lungs. However, an initial clinical presentation involving spinal or multiple bone metastases in patients with thymic carcinoma is extremely rare. We experienced two cases of thymic carcinoma that initially presented with spinal compression and severe pain due to multiple bone metastases, respectively. Both patients were histologically diagnosed with metastatic thymic squamous cell carcinoma based on the findings of specimens resected from the metastatic bone lesions. We herein describe the clinical courses of these cases and review the characteristics of bone metastasis of thymic carcinoma.

Late relapse of extranodal natural killer/T cell lymphoma, nasal type, after more than ten years

Extranodal NK/T cell lymphoma, nasal type (ENKL) is a malignant lymphoproliferative disorder of NK cells characterized by an invasive nature with vascular damage and necrosis [1–3]. The upper aerodigestive tracts, especially nasal cavities, are commonly involved (the nasal type), and in minor populations, other sites such as the skin, intestines, or soft tissues other than the aerodigestive tracts are the main invasive sites (extranasal type). ENKL is more prevalent in Asians and Central Americans, and a lower incidence among Caucasians is recognized. ENKL is also characterized by a strong association with Epstein-Barr virus (EBV). The clinical outcome of ENKL varies depending on the involved site and clinical stage, and the prognosis is considerably worse than that of other lymphomas, although the recent therapeutic progress including in concurrent chemoand radiotherapy against limited-stage nasal type ENKL and the introduction of hematopoietic cell transplantation (HCT) might improve the outcome [4–6]. Some cases of ENKL have been known to relapse after a long duration of complete response [7,8]; however, the biological mechanisms of ENKL including those of such cases are still unknown. Here, we report three Japanese cases of ENKL who relapsed after a period of longer than 10 years of complete response after the initial treatment. Case one was a 44-year-old male who had suffered from intermittent nasal discharge and was diagnosed with non-Hodgkin lymphoma, diffuse pleomorphic type, with clinical stage IIE in 1991. He had received combination chemotherapy of methotrexate (MTX), doxorubicin (ADR), cyclophosphamide (CY), vincristine (VCR), and bleomycin (MACOP-B) and local irradiation. He achieved complete response (CR) and had been well until 2007, when he noticed hoarseness and was found to have a paralaryngeal tumor. The tumor was diagnosed as ENKL with positivity for cytoplasmic CD3, CD56, TIA1, granzyme B, and EBV by immunohistochemical studies and in situ hybridization, respectively. He needed trachostomy for bronchial obstruction, and multiple skin lesions also developed. He was administered carboplatin, etopside, ifosdamide (IFO), and dexamethasone, with no improvement, so he was also given cytosine arabinoside, IFO, MTX, and L-asparaginase. He reached CR after three courses of chemotherapy. Months later, he died of exacerbation of his ENKL. Re-examination of the histological specimen of the primary lesion taken in 1991 revealed identical morphological features and the same immunophenotypes and EBV positivity as the relapsed lesions. He was clarified as having had a relapse of ENKL after 16 years. The second case was a 36-year-old female who was diagnosed with, diffuse, medium sized, NHL, which was positive for CD45RO and negative for CD20, in a right nasal tumor in 1989. She received four courses of MACOP-B and 50 Gy involved field irradiation (IFR). She had maintained a CR until

External-Beam Radiotherapy for Localized or Locally Advanced Prostate Cancer in Japan: A Multi-Institutional Outcome Analysis

BACKGROUNDnThe outcomes of patients with localized or locally advanced prostate cancer treated with external-beam radiotherapy are not well known in Japan.nnnMETHODSnThirty-four institutions combined data on 679 patients with localized or locally advanced prostate cancer treated with a total dose >/=60 Gy between 1995 and 2002.nnnRESULTSnWith a median follow-up of 46 months, the 5-year overall, clinical progression-free, and biochemical relapse-free survival rate were 93.0, 95.3 and 71.9% for all patients, respectively. The 5-year progression-free, and biochemical relapse-free survival rates according to the risk group were 100%, 90.8% in the low-risk group, 98.3%, 75.7% in the intermediate-risk group and 93.6%, 67.6% in the high-risk group, respectively. The multivariate analysis for biochemical relapse-free survival revealed that prostate-specific antigen (relative risk, 1.002; 95% CI, 1.001-1.003; P = 0.0041), Gleason score (relative risk, 1.166; 95% CI, 1.046-1.302; P = 0.0055), T classification (relative risk, 2.897; 95% CI, 1.999-4.230; P = 0.0000), pelvic irradiation (relative risk, 2.042; 95% CI, 1.328-3.273; P = 0.0008), and androgen abletion (relative risk, 0.321; 95% CI, 0.240-0.427; P = 0.0000) were significant prognostic factors. Only 1.1% of patients experienced late morbidity of Grade 3.nnnCONCLUSIONnRadiotherapy for prostate cancer seemed to be effective, with little risk of normal tissue complications.

Radiotherapy following mastectomy: indication and contraindication of chest wall irradiation

PURPOSEnTo determine in which cases radiotherapy of the chest wall following mastectomy is indicated, based on the local recurrent rate in patients with locally advanced breast cancer.nnnMETHODS AND MATERIALSnFrom 1984 until 1994, 105 patients who had four or more histopathologically confirmed axillary nodes metastases, or T3-4Nany, were subjected to mastectomy and were administered radiotherapy postoperatively using the hockey-stick field, which included the ipsilateral supraclavicular fossa and internal mammary nodes, except the chest wall. Median age was 51 years old (range, 23 to 82 years old). Eighty-five patients underwent radical mastectomy, 18 modified radical mastectomy, and 2 extended radical mastectomy. Fraction size was 2 Gy/day, the weekly fraction size was 10 Gy and the total dose ranged from 44 Gy to 54 Gy (median 50 Gy). Seventy-four patients were administered adjuvant chemotherapy, and 61 patients were administered hormone therapy.nnnRESULTSnThe 5-year disease-free survival rates of the whole study population were 66%. The 5-year chest wall recurrence rates were 10%. The 5-year chest wall recurrence rates of the patients who had no vascular invasion (n = 19) and the patients who had definite vascular invasion (n = 38) were 0% and 24%, respectively (p = 0.036). All the patients who presented chest wall recurrence had four or more axillary nodes metastases. Nine of the 10 patients who presented chest wall recurrence had definite vascular invasion, while there was no information about vascular invasion for the remaining patient. Factors such as age, pathological subtypes, tumor location, estrogen receptors, extent of resection, chemotherapy, and hormone therapy did not influence the development of chest wall recurrence.nnnCONCLUSIONnAmong patients with breast cancer who have four or more positive axillary nodes or T3-4Nany, those who have no vascular invasion or less than 4 axillary nodes metastases do not need to be subjected to chest wall irradiation after radical mastectomy.

Alectinib-Induced Alopecia in a Patient with Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer

Alectinib, a novel alternative anaplastic lymphoma kinase (ALK) inhibitor, is highly effective against ALK-positive non-small cell lung cancer (NSCLC) and is well tolerated. Molecular targeted agents generally have little contribution to alopecia. We encountered a case of alopecia that developed gradually over 2 months after initiation of alectinib administration for the treatment of ALK-positive NSCLC. The patient had no history of alopecia in previous treatments of cisplatin + pemetrexed and crizotinib. The present case indicates that alopecia should be taken into consideration as toxicity during alectinib treatment, which could adversely affect the psychological and emotional condition and quality of life even in patients treated with specific molecular targeted agents.