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Biomedical subjects

W J Koh

Publications and source records attributed to W J Koh.

At least 19 recordsLinked to original sources

Pulmonary TB and NTM lung disease: comparison of characteristics in patients with AFB smear-positive sputum.

OBJECTIVE: To compare the clinical and radiographic features of pulmonary tuberculosis (PTB) and non-tuberculous mycobacteria (NTM) lung disease in patients with acid-fast bacilli (AFB) positive sputum specimens. DESIGN: The initial clinical and radiographic features of 229 PTB patients were compared with those of 70 patients with NTM lung disease. The most commonly involved organisms in the NTM lung disease cases were Mycobacterium avium complex (n = 38, 54%) and M. abscessus (n = 26, 37%). RESULTS: Clinical and radiographic findings that were more common in patients with NTM lung disease than in PTB patients were: older age (P < 0.001), non-smoker (P < 0.001), history of previous TB treatment (P < 0.001), absence of pleural effusion (P = 0.017), involvement of middle and/or lower lung zones (P = 0.007), and bilateral disease (P = 0.005). Multivariate analysis showed that older age (> or = 40 years), non-smoker, previous TB treatment, absence of pleural effusion and involvement of middle and/or lower lung zones were significant independent predictors for NTM lung disease. CONCLUSIONS: There is considerable overlap in the clinical and radiographic appearances of PTB and NTM lung disease. The isolation and identification of causative organisms are mandatory for a correct diagnosis in patients with AFB-positive sputum specimens.

Coloring Agents↗

Recovery rate of NTM from AFB smear-positive sputum specimens at a medical centre in South Korea.

OBJECTIVE: To investigate the recovery rate of non-tuberculous mycobacteria (NTM) from acid-fast bacilli (AFB) smear-positive sputum specimens at a tertiary care medical centre in South Korea with a high pulmonary tuberculosis (PTB) burden. DESIGN: Retrospective analysis of data from AFB smear- and culture-positive sputum specimens collected between January 1998 and December 2001. RESULTS: Over 4 years, 1328 sputum specimens collected from 616 patients were AFB smear- and culture-positive. NTM were recovered from 9.1% (121/1328) of the smear-positive sputum specimens, and from 8.1% (50/616) of patients with smear-positive sputum. NTM were isolated at least twice in 94% (47/50) of the patients from whom NTM was recovered. The most common organism found was Mycobacterium avium complex, followed by M. abscessus. CONCLUSION: These results suggest that a substantial proportion of patients at a tertiary care medical centre in South Korea with AFB smear-positive sputum specimens may have NTM lung disease rather than PTB.

Adult↗

Neutron radiotherapy for recurrent pleomorphic adenomas of major salivary glands.

INTRODUCTION: Pleomorphic adenoma is the most common neoplasm arising in the salivary glands. Surgical management is the primary therapeutic modality. With the use of modern surgical techniques, recurrence is infrequent, and facial nerve sparing is the norm. However, for patients with recurrent disease, the risk of further relapses is increased with surgical resection alone, particularly for those patients in whom multiple recurrences have already occurred. The role of adjuvant radiotherapy in this setting remains uncertain. Although neutron radiotherapy is superior to conventional radiotherapy for malignant salivary gland tumors, its role in the treatment of pleomorphic adenomas is less well defined. We report our experience using this modality for high-risk, recurrent pleomorphic adenomas. METHODS: Sixteen patients were treated with neutron radiotherapy for recurrent pleomorphic adenomas of major salivary glands from 1986 through 1993. The median age at diagnosis was 33 years (range, 11-77 years); median age at the time of neutron radiotherapy was 52 years (range, 22-77 years); median number of prior surgical procedures was 3 (range, 1-6); median duration from initial diagnosis to radiotherapy was 14.5 years (range, 3 months-30 years); median follow-up was 83 months (range, 9-144 months). The median period at risk for survivors was 96 months (defined as the interval from completion of neutron radiotherapy to last follow-up). Ten patients had evidence of gross residual disease at the time of treatment as determined by imaging studies, with nine patients having multinodular disease. RESULTS: The 10-year actuarial survival was 79%. One patient died from lung metastases 9 months after treatment; one patient died from a liver tumor of uncertain origin, but the histology could not rule out a metastasis from the previous pleomorphic adenoma; and one patient died from recurrent disease at the base of skull. The 15-year actuarial locoregional control rate was 85%. One of the two patients with locoregional recurrence had a malignant transformation into an adenocarcinoma. No statistical difference in 15-year actuarial survival (75% vs 83%, p =.82) was found comparing patients with gross residual disease vs microscopic residual disease. The actuarial 15-year locoregional control was 76% for patients with gross residual disease vs 100% for those with microscopic disease. The 15-year actuarial risk of RTOG/ESTRO nonaudiologic grade III/IV complications was 21%. No facial nerve injuries were observed as a direct consequence of neutron radiotherapy. CONCLUSIONS: Neutron radiotherapy offers both excellent local control rates and survival rates in patients with multiply recurrent pleomorphic adenomas that are not candidates for surgical resection, even in the presence of gross residual disease. The treatment-related morbidity is acceptable. Malignant transformations and metastases, although uncommon, may be observed in this tumor.

Adenoma, Pleomorphic↗

Palliative radiation therapy for gynaecological malignancies.

Patients with advanced, recurrent, or metastatic gynaecological malignancies constitute a heterogenous population with diverse symptomatology. Progressive abdominopelvic disease can result in vaginal or diffuse pelvic bleeding, pain, and visceral or lymphovascular obstruction. Gynaecological cancer can also develop debilitating metastases, in particular to bone, central nervous system, or chest. Radiation therapy is a local-regional treatment modality, that, when applied judiciously, can lead to substantial symptomatic relief and tumour response. Individualized application is necessary, balancing efficacy and patient convenience versus treatment intensity, expected duration of palliation and potential toxicity. Important factors to consider are a patient's performance status, extent and sites of tumour, specific symptoms, and life expectancy. The optimal incorporation of radiotherapy is best achieved in the context of a multidisciplinary approach that addresses all facets of palliative care in patients with incurable gynaecological malignancies, to maximize their quality of life and functional level.

Bone Neoplasms↗

Radiation therapy in endometrial cancer.

The role of radiation in endometrial cancer, especially in the adjuvant setting, is controversial. Factors that influence radiotherapy recommendations include surgical considerations, pathological findings, potential sites of disease recurrence and the practice philosophies of the individual physician. It has been demonstrated that adjuvant radiotherapy following primary surgery significantly improves pelvic tumour control, but has no measurable impact on overall survival in an unselected patient population. Studies to date have been hampered by the inclusion of patients with a wide spectrum of prognostic features; this may decrease the likelihood of observing greater benefit in discriminate subsets at higher risk of relapse. Further trials are required to define clinical prognosis more precisely and to investigate the role of radiation in higher-risk patients. In the meantime, we propose guidelines for radiotherapy in endometrial cancer which serve as bases for discussion and collaboration among physicians and as platforms for future study and progress.

Brachytherapy↗

Endobronchial brachytherapy.

High-dose rate endobronchial brachytherapy is a well-tolerated out-patient procedure that provides a high likelihood for durable palliation of symptoms associated with endobronchial tumor. The most significant associated toxicity is late massive hemoptysis, the risk for which can be minimized by careful treatment planning and limiting the size of the delivered dose per fraction to less than 10 Gy, prescribed at 1 cm distance.

Brachytherapy↗

The prognostic significance of radiation dose and residual tumor in the treatment of barrel-shaped endophytic cervical carcinoma.

OBJECTIVE: The aim of this study was to evaluate the impact of total radiation dose on residual tumor and the prognostic significance of persistent disease in women with bulky, barrel-shaped cervical carcinoma who received definitive radiation followed by adjuvant hysterectomy. METHODS: The medical records of 57 patients with bulky endophytic cervical carcinoma treated at the University of Washington between 1976 and 1997 were reviewed. All patients received external beam pelvic radiotherapy supplemented by intracavitary brachytherapy, followed by extrafascial hysterectomy 6 to 8 weeks later. RESULTS: The mean pretreatment tumor diameter was 5.9 cm, with a range of 4-9 cm. Total radiation dose to point A ranged from 5040 to 9700 cGy, and the mean for the group was 7966 cGy. Residual disease was present in 35 (61%) of the hysterectomy specimens. The frequency of cervical tumor sterilization correlated significantly with the mean radiation dose to point A (P = 0.016). Patients without histologic residual disease had a significantly improved outcome, with 95% of patients remaining clinically free of disease at last follow-up, versus 31% of those with residual disease (P < 0.001). As expected, the pelvic control rate was excellent (100%) in patients with complete tumor eradication compared to the group with residual tumor (44%). Those with no residual disease enjoyed a significantly improved survival compared to those with residual tumor (P < 0.001). Furthermore, a statistically significant higher survival was realized in patients harboring only microscopic residual compared to those with either macroscopically evident tumor residuum and/or positive surgical margins (P = 0.036). CONCLUSIONS: Higher radiation doses are associated with an improved likelihood of tumor eradication in the treatment of bulky, endophytic cervical cancer and complete tumor sterilization at adjuvant hysterectomy is predictive of significantly enhanced survival and pelvic control. The high rate of histologic tumor persistence in our series emphasizes the need for more efficacious therapies in patients with bulky endophytic cervical cancer and argues for escalation of radiation dose even when adjuvant hysterectomy is planned.

Adult↗

Adjuvant therapy for high-risk, early stage cervical cancer.

The identification of various pathologic risk factors after primary surgical management of early stage cervical cancer portends a higher rate of relapse and decreased survival. Historical attempts to improve outcome focused mainly on the use of adjuvant pelvic radiation, with limited success overall. Analysis of patterns of failure after radical hysterectomy led to better stratification of patients into risk groups and incorporated testing of systemic agents in those considered at high risk of distant failure. Two recently reported randomized, clinical trials have greatly advanced our understanding of the role of postoperative therapy in cervix cancer. In patients with positive nodes, the use of combined adjuvant chemotherapy and radiation significantly improves relapse-free survival and overall survival, compared with radiation alone. For node-negative patients with other primary tumor risk features, pelvic radiation significantly improves relapse-free survival, compared with no further therapy. An observed improvement in survival for irradiated patients awaits statistical confirmation after maturation of the data. Further improvements in adjuvant therapy for high risk, early stage cervical cancer will come from enhanced definition of prognostic variables, better patient selection, and refinements in both local and systemic therapies.

Combined Modality Therapy↗

A new technique for performing Syed template interstitial implants for anterior vaginal tumors using an open retropubic approach.

The Syed template (Alpha-Omega Services, Bellflower, CA) has been established as an advance in interstitial gynecologic brachytherapy. Unfortunately, enthusiasm for the technique is often tempered by certain tumor geometries which require blind insertion of the interstitial needles, potentially risking inaccurate placement of the radioactive sources and viscus perforation. These concerns arise particularly in the management of anterior vaginal tumors where difficulties in negotiating the pubic arch can prevent optimal needle placement. In answer to this problem, a technique utilizing an open retropubic approach for Syed template interstitial implants in anterior vaginal tumors under direct visualization is described. To date, six procedures have been performed. The disease entities include advanced cervical squamous cell carcinoma, clear cell carcinoma of the vagina, recurrent vaginal carcinoma, recurrent endometrial carcinoma, and urethral adenocarcinoma. Complete response was noted in five of six patients but persistent local control of disease was achieved in only one of five complete responses over a relatively short follow-up interval. Complications included paravaginal abscess (n = 1), postoperative deep venous thrombosis (n = 1), abdominal incision cellulitis (n = 1), and radiation enteritis (n = 1). An open retropubic approach allows direct visualization of the bladder and urethra during interstitial implantation of anterior vaginal malignancies and facilitates negotiation of the pubic arch. In our experience, this technique results in improved needle positioning and is thus intuitively likely to aid in avoiding injury to surrounding normal tissues. Additional accrual of a larger cohort will be necessary to arrive at any meaningful objective conclusions regarding the technique's benefit over current modalities.

Adult↗

Impact of surgical staging in women with locally advanced cervical cancer.

OBJECTIVE: The aim of this study was to evaluate the impact of surgical staging in the treatment and outcome of women with locally advanced cervical cancer. METHODS: Ninety-eight women with locally advanced cervical cancer treated between 1993 and 1997 were retrospectively reviewed. Survival probabilities were calculated by the Kaplan-Meier product limit method and compared with the log-rank test. RESULTS: Of the 98 women treated over the 5-year period, 86 were surgically staged: 61 by a retroperitoneal approach, 18 by laparoscopy, and 7 by laparotomy. Median blood loss was 120 cc and median length of hospitalization was 3 days. Preoperative CT scans (n = 55), when compared with surgical findings, missed macroscopic nodal disease in 20% and microscopic disease in 15% and overcalled disease in 10% of cases. Lymph node metastases were found in 45/86 patients (52%): 12 microscopic and 33 macroscopic. The highest level of nodes found to be involved was pelvic in 23, common iliac nodes in 3, para-aortic nodes in 14, and scalene nodes in 5 cases. Of the 86 patients, 49 received pelvic radiation, 27 received extended field radiation, and 10 were identified for palliative treatment only (5 scalene node metastasis, 5 extensive intraperitoneal disease). For node-negative patients, 5-year survival was 74%; for microscopic nodal involvement it was 58%; and for macroscopic involvement it was 39% (P = 0.007). Five-year survival for women with para-aortic node involvement was 52%. Number of nodes involved was a significant prognostic variable (P = 0.008). Patients who received chemotherapy had a 5-year survival of 68% compared to 35% for those who did not (P = 0.06). Factors which did not affect survival included age, histology, type of surgery, stage, and type of radiation (pelvic vs extended). CONCLUSION: Surgical staging of women with locally advanced cervical cancer can be performed with acceptable morbidity and it provided more accurate information than CT scans and resulted in a modification of the standard pelvic radiation field for 43% of our patients. The information obtained from surgical staging allows better individualization of therapy, which may improve overall clinical outcome.

Adult↗

Pretreatment scalene node biopsy in gynecologic malignancy: prudent or passé?

OBJECTIVES: Surgicopathologic evaluation of the scalene fat pad is considered a critical step in the pretreatment evaluation of patients at our institution with cervical or corpus carcinoma when the periaortic lymph nodes (PAN) are involved. However, enthusiasm for this procedure at other centers has waned, largely due to a wide discrepancy in the reported rates of occult scalene node involvement. In an attempt to clarify the benefit of pretreatment scalene node sampling in gynecologic malignancies, we present our experience over the past 18 years. MATERIALS AND METHODS: We identified 57 patients who underwent scalene node sampling between 1980 and 1998. In 39 of 49 (80%), the decision to proceed with scalene node sampling was based entirely on histologically documented PAN metastases. In the remainder, scalene node sampling was prompted by the presence of suspicious clinical findings. RESULTS: Of the 49 patients included in the study, 33 had carcinoma of the cervix, while 16 had corpus carcinoma. Ninety percent of scalene node sampling was performed at the time of primary diagnosis. Overall, 9 patients (18%) had scalene node metastases. Notably, not a single patient with corpus cancer was found to have scalene node metastases in the absence of clinically evident scalene node enlargement independent of PAN status. In cervix cancer cases, the presence of grossly involved PAN was predictive of a high likelihood of scalene node metastases (44%), while no patient with occult PAN metastases had involvement of the scalene node. Only 1 minor complication was encountered following scalene node sampling. The 40 scalene node-negative patients were treated with either extended field radiation or whole abdominal radiation therapy, and 20% developed a major, RTOG grade >/=3 complication such as fistula formation, bowel obstruction, or ureteral stenosis. Only 1 case of mild radiation enteritis and cellulitis occurred during palliative radiation in the group of patients with scalene node metastases. CONCLUSIONS: Scalene node sampling may be of benefit in the pretreatment evaluation of patients with cervical carcinoma when PAN are grossly involved. Given that scalene node involvement satisfies the criteria for distant metastases, identification of such allows the clinician to avoid the morbidity of extended field radiotherapy in a setting without the chance for cure.

Biopsy↗

Uterine papillary serous carcinoma: evaluation of long-term survival in surgically staged patients.

OBJECTIVE: Earlier studies have demonstrated that the uterine papillary serous carcinoma (UPSC) variant of endometrial carcinoma has a high recurrence rate, even when disease is apparently confined to the uterus. The current study evaluated survival in patients with surgically staged UPSC. METHODS: Patients with UPSC were identified from surgical pathology files and charts were retrospectively reviewed. Only patients who had undergone a TAH-BSO, lymph node dissection, and peritoneal cytology were included. RESULTS: The FIGO stages of the 36 patients were 12 Stage I (4 IA, 4 IB, 4 IC), 2 Stage IIB, 13 Stage III (5 IIIA, 8 IIIC), and 9 Stage IV. Of the 14 Stage I/II patients, 6 did not receive adjuvant therapy, 5 received whole pelvic radiation (WPXRT), and 3 received whole abdominal radiation therapy (WART); after a median follow-up interval of 50 months only 2 (14%) of these Stage I/II patients have developed a recurrence. Both of the recurrences were in Stage IC patients who received radiation; 1 recurred in the radiation field. Of the 5 Stage IIIA patients, 3 patients declined therapy and 2 were treated with WART; 3 patients, including the 2 who received radiation therapy, are alive without disease. Of the 8 Stage IIIC patients, 2 declined postoperative therapy, 2 received WART, and 4 received WPXRT with an extended field to include paraaortic nodes. Four of the 6 Stage IIIC patients treated with curative intent are without evidence of disease and 1 died of unrelated causes after a median follow-up interval of 48 months. Both of the Stage IIIC patients who declined treatment recurred. Of the 9 patients with Stage IV disease, 8 have died of disease. CONCLUSION: Women with UPSC have a good prognosis when surgical staging confirms that disease is confined to the uterus (Stage I/II). Surgical findings can also be used to tailor adjuvant radiation treatments. Further study is required to define the optimal treatment for women with metastatic UPSC.

Aged↗

Fast neutrons in prostatic adenocarcinomas: worldwide clinical experience.

Primary tumor control remains a major problem in the treatment of locally advanced prostate carcinoma. Clinical local failure rates approach 30-40% and may be significantly higher when results of prostatic biopsy or prostate-specific antigen (PSA) levels are considered. The low growth rate and cycling fraction of prostate adenocarcinoma suggest potential therapeutic advantage for the high linear energy transfer (LET) of neutrons. The Radiation Therapy Oncology Group (RTOG) performed a multi-institutional randomized trial (RTOG 77-04) comparing mixed beam (neutron plus photon) irradiation to conventional photon irradiation for the treatment of locally advanced prostate cancer. A subsequent trial by the Neutron Therapy Collaborative Working Group (NTCWG 85-23) compared pure neutron irradiation to standard photon irradiation. Both randomized trials demonstrate significant improvement in locoregional control with neutron irradiation compared to conventional photon irradiation in the treatment of locally advanced prostate carcinoma. To date, only the mixed beam trial has shown a significant survival benefit. Future analysis of the larger NTCWG trial at the 10-year point should confirm whether or not improved locoregional control translates into a survival advantage. These findings have significant implications for all local treatment strategies including dose-escalated conformal photon irradiation, prostate implantation, and neutron radiation. Given the large numbers of patients afflicted with this disease, a positive survival advantage for neutrons or mixed beam therapy would provide a strong incentive for the development of economically feasible clinical neutron facilities.

Adenocarcinoma↗

Fluorine-18-fluoromisonidazole radiation dosimetry in imaging studies.

UNLABELLED: Fluoromisonidazole (FMISO), labeled with the positron emitter 18F, is a useful hypoxia imaging agent for PET studies, with potential applications in patients with tumors, cardiovascular disease and stroke. METHODS: Radiation doses were calculated in patients undergoing imaging studies to help define the radiation risk of FMISO-PET imaging. Time-dependent concentrations of radioactivity were determined in blood samples and PET images of patients following intravenous injection of [18F]FMISO. Radiation absorbed doses were calculated using the procedures of the Medical Internal Radiation Dose (MIRD) committee, taking into account the variation in dose based on the distribution of activities observed in the individual patients. As part of this study we also calculated an S value for brain to eye. Effective dose equivalent was calculated using ICRP 60 weights. RESULTS: Effective dose equivalent was 0.013 mSv/MBq in men and 0.014 mSv/MBq in women. Individual organ doses for women were not different from men. Assuming bladder voiding at 2- or 4-hr intervals, the critical organ that received the highest dose was the urinary bladder wall (0.021 mGy/MBq with 2-hr voiding intervals or 0.029 mGy/MBq with 4-hr voiding intervals). CONCLUSION: The organ doses for [18F]FMISO are comparable to those associated with other commonly performed nuclear medicine tests and indicate that potential radiation risks associated with this study are within generally accepted limits.

Female↗

The potential role of external beam radiation in preventing restenosis after coronary angioplasty.

The potential role of radiation in the prevention of coronary artery restenosis after angioplasty has generated much recent interest. Animal research and pilot clinical efforts have focused primarily on intraluminal methods of radiation delivery. This article reviews the experience to date with external beam radiation in restenosis prevention and suggests issues that should be considered from the standpoint of both external beam and intravascular radiotherapy. External beam radiation can certainly play an effective role in clinical studies of coronary artery restenosis, and a multicenter randomized trial of external beam radiation after coronary angioplasty has been initiated.

Angioplasty, Balloon, Coronary↗

Quantifying regional hypoxia in human tumors with positron emission tomography of [18F]fluoromisonidazole: a pretherapy study of 37 patients.

PURPOSE: To assess pretreatment hypoxia in a variety of tumors using positron emission tomography (PET) after injection of the hypoxia-binding radiopharmaceutical [18F]fluoromisonidazole ([18F]FMISO). METHODS AND MATERIALS: Tumor fractional hypoxic volume (FHV) was determined in 21 nonsmall cell lung cancer patients, 7 head and neck cancer patients, 4 prostate cancer patients, and 5 patients with other malignancies by quantitative PET imaging after injection of [18F]FMISO (0.1 mCi/kg). The FHV was defined as the proportion of pixels in the imaged tumor volume with a tissue:blood [18F] activity ratio > or = 1.4 at 120-160 min postinjection. A FHV > 0 was taken as evidence for tumor hypoxia. RESULTS: Hypoxia was observed in 36 of 37 tumors studied with FMISO PET imaging; FHVs ranged from 0 to 94.7%. In nonsmall cell lung cancers (n = 21), the median FHV was 47.6% and the range, 1.3 to 94.7%. There was no correlation between tumor size and FHV. In the seven head and neck carcinomas, the median FHV was 8.8%, with a range from 0.2 to 18.9%. In the group of four prostate cancers, the median and range were 18.2% and 0 to 93.9%, while in a group of five tumors of different types the median FHV was 55.2% (range: 21.4 to 85.8%). CONCLUSIONS: Hypoxia was present in 97% of the tumors studied and the extent of hypoxia varied markedly between tumors in the same site or of the same histology. Hypoxia also was distributed heterogeneously between regions within a single tumor. These results are consistent with O2 electrode measures with other types of human tumors. The intra- and intertumor variability indicate the importance of making oxygenation measures in individual tumors and the necessity to sample as much of the tumor volume as possible.

Carcinoma, Non-Small-Cell Lung↗

Neutron radiotherapy for adenoid cystic carcinoma of minor salivary glands.

PURPOSE: To examine the efficacy of fast neutron radiotherapy for the treatment of patients with locally advanced, adenoid cystic carcinoma of minor salivary glands and to identify prognostic variables associated with local control, overall survival, and cause specific survival. METHODS AND MATERIALS: Eighty-four patients having adenoid cystic carcinoma of minor salivary glands were treated with fast neutron radiotherapy during the years 1985-1994. All patients had either unresectable disease or gross disease remaining after attempted surgical extirpation. Seventeen patients had previously received conventional radiotherapy and their subsequent treatment fields and doses for neutron radiotherapy were modified for critical sites (brainstem, spinal cord, brain). Although the median doses (tumor maximum and tumor minimum) only varied by < or = 10%, treatment portals were substantially smaller in these patients because of normal tissue complication considerations. Twelve patients (13%) had distant metastases at the time of treatment and were only treated palliatively with smaller treatment portals and lower median tumor doses (< or = 80% of the doses delivered to curatively treated patients). Seventy-two patients were treated with curative intent, with nine of these having recurrent tumors after prior full-dose radiotherapy. The median duration of follow-up at the time of analysis was 31.5 months (range 3-115). Sites of disease and number of patients treated per disease site were as follows: paranasal sinus-31; oral cavity-20; oropharynx-12; nasopharynx-11; trachea-6; and other sites in the head and neck-4. RESULTS: The 5-year actuarial local-regional tumor control rate for all patients treated with curative intent was 47%. Patients without involvement of the cavernous sinus, base of skull, or nasopharynx (51 patients) had a 5-year actuarial local-regional control rate of 59%, whereas local-regional control was significantly lower (15%) for patients with tumors involving these sites (p < 0.005). In the latter cases, normal tissue injury considerations precluded delivery of the full dose to the entire tumor. Patients with no history of prior radiotherapy (63 patients) had an actuarial local control rate of 57% at 5 years compared to 18% for those (9 patients) who had been previously irradiated with conventional photons (p = 0.018). Eliminating the dose-limiting factors of prior radiation therapy and/or high risk sites of involvement, the 5-year actuarial local-regional control rate for these 46 patients was 63%, with an actuarial cause specific survival rate of 79%. Lymph node status was a predictor of distant metastasis: 57% of node positive patients developed distant metastases by 5 years compared to 15% of patients with negative nodes (p < 0.0005), and patients who had nodal involvement developed distant metastases sooner than node negative patients (p < 0.0001). The 5-year actuarial overall survival and cause specific survival for the 72 patients treated with curative intent were 59% and 64%, respectively. CONCLUSIONS: Fast neutron radiotherapy offers high local-regional control and survival rates for patients with locally advanced, unresectable adenoid cystic carcinomas of minor salivary glands. It should be considered as initial primary treatment for these patients, as well as for other patients in whom surgical extirpation would cause considerable morbidity.

Adolescent↗

Effect of high-dose pentoxifylline on acute radiation-induced lung toxicity in a rat lung perfusion model.

PURPOSE: The purpose of this study was to study the effect of high-dose oral pentoxifylline on radiation-induced acute lung injury as assessed with a rat lung perfusion model. METHODS AND MATERIALS: Adult male Sprague-Dawley rats were used throughout this study. A preliminary experiment determined that treatment with 2 g/liter pentoxifylline in drinking water resulted in an average consumption of 1.38 g/m2/day, which is comparable to the maximum tolerated dosage in humans. Seventy-two rats were irradiated to the left hemithorax with single fraction doses ranging from 10 through 18 Gy. Half were treated with 2 g/liter pentoxifylline in drinking water from 1 week before radiation through 8 weeks after radiation. Lung vascular perfusion scanning was performed at 3, 4, 5, 6, and 8 weeks after radiation using 99mTc-macroaggregated albumin. The lung perfusion ratio was defined as the number of counts due to radioactivity within the irradiated left lung region of interest divided by the number of counts within the region of the nonirradiated right lung. This lung perfusion ratio has been shown to decrease with radiation-induced lung injury. RESULTS: Although radiation led to a decreased lung perfusion ratio in all groups, those receiving pentoxifylline maintained higher ratios than irradiated controls from 3-5 weeks, especially for those receiving 15 or 18 Gy. However, from 6 through 8 weeks the irradiated controls exhibited partial recovery of lung perfusion ratio, whereas the pentoxifylline groups did not. By 8 weeks after 15 and 18 Gy, lung perfusion ratios were significantly higher for the irradiated controls than for pentoxifylline-treated rats-a reversal of the pattern observed at 3-5 weeks. CONCLUSIONS: The protection by pentoxifylline against radiation-induced acute lung injury was transient and limited to the first 5 weeks after radiation. Subsequent recovery from lung injury was inhibited by this drug at later times within the acute phase.

Acute Disease↗