Expanding the horizons of histoplasmosis: disseminated histoplasmosis in a renal transplant patient after a trip to Bangladesh.

Histoplasmosis is recognized to occur in the Ohio and Mississippi River Valleys of the United States, but less widely appreciated is its worldwide distribution. We report a case of disseminated histoplasmosis with disease involving skin, lungs, and epiglottis in a renal transplant patient 6 months after a trip to Bangladesh, to highlight the potential risk of acquisition of this infection in the Indian subcontinent.

Posttreatment Imaging in Patients with Head and Neck Cancer without Clinical Evidence of Recurrence: Should Surveillance Imaging Extend Beyond 6 Months?

BACKGROUND AND PURPOSE: Early detection of residual or recurrent disease is important for effective salvage treatment in patients with head and neck cancer. Current National Comprehensive Cancer Network guidelines do not recommend standard surveillance imaging beyond 6 months unless there are worrisome signs or symptoms on clinical examination and offer vague guidelines for imaging of high-risk patients beyond that timeframe. Our goal was to evaluate the frequency of clinically occult recurrence in patients with head and neck squamous cell carcinoma with positive imaging findings (Neck Imaging Reporting and Data Systems scores of 2-4), especially after 6 months. MATERIALS AND METHODS: This institutional review board-approved, retrospective data base search queried neck CT reports with Neck Imaging Reporting and Data Systems scores of 2-4 from June 2014 to March 2018. The electronic medical records were reviewed to determine outcomes of clinical and radiologic follow-up, including symptoms, physical examination findings, pathologic correlation, and clinical notes within 3 months of imaging. RESULTS: A total of 255 cases, all with Neck Imaging Reporting and Data Systems scores of 2 or 3, met the inclusion criteria. Fifty-nine patients (23%) demonstrated recurrence (45 biopsy-proven, 14 based on clinical and imaging progression), and 21 patients (36%) had clinically occult recurrence (ie, no clinical evidence of disease at the time of the imaging examination). The median overall time to radiologically detected, clinically occult recurrence was 11.4 months from treatment completion. CONCLUSIONS: Imaging surveillance beyond the first posttreatment baseline study was critical for detecting clinically occult recurrent disease in patients with head and neck squamous cell carcinoma. More than one-third of all recurrences were seen in patients without clinical evidence of disease; and 81% of clinically occult recurrences occurred beyond 6 months.

Variable ultrasound echogenicity in flowing blood.

Real-time ultrasound imaging of large abdominal veins revealed bloodstream echogenicity of variable intensity. This variability is largely due to the entrance and persistance of tributary blood currents that show different echogenicity. Red cell aggregation is probably an important cause of bloodstream echoes and their variable intensity.

Measurement of circulating tumor cells in squamous cell carcinoma of the head and neck and patient outcomes.

OBJECTIVES: We report the outcomes of patients with squamous cell carcinoma of the head and neck (HNSCC) whose circulating tumor cells (CTCs) were quantified using surface-enhanced Raman scattering (SERS) nanotechnology. METHODS: SERS tagged with EGF was used to directly measure targeted CTCs. Patient charts were retrospectively reviewed. An optimal cut point for CTCs in 7.5 ml of peripheral blood predictive of for distant metastasis-free survival (DMFS) was identified by maximizing the log-rank statistic. An ROC analysis was also performed. RESULTS: Of 82 patients, 13 experienced metastatic progression. The optimal cut point for DMFS was 675 CTCs (p = 0.047). For those with distant recurrence (n = 13) versus those without distant recurrence (n = 69), the CTC cut point which results in the largest combined sensitivity and specificity values is also 675 (sensitivity = 69%, specificity = 68%). CONCLUSION: Liquid biopsy techniques in HNSCC show promise as a means of identifying patients at greater risk of disease progression.

Initial Performance of NI-RADS to Predict Residual or Recurrent Head and Neck Squamous Cell Carcinoma.

BACKGROUND AND PURPOSE: The Head and Neck Imaging Reporting and Data System (NI-RADS) surveillance template for head and neck cancer includes a numeric assessment of suspicion for recurrence (1-4) for the primary site and neck. Category 1 indicates no evidence of recurrence; category 2, low suspicion of recurrence; category 3, high suspicion of recurrence; and category 4, known recurrence. Our purpose was to evaluate the performance of the NI-RADS scoring system to predict local and regional disease recurrence or persistence. MATERIALS AND METHODS: This study was classified as a quality-improvement project by the institutional review board. A retrospective database search yielded 500 consecutive cases interpreted using the NI-RADS template. Cases without a numeric score, non-squamous cell carcinoma primary tumors, and primary squamous cell carcinoma outside the head and neck were excluded. The electronic medical record was reviewed to determine the subsequent management, pathology results, and outcome of clinical and radiologic follow-up. RESULTS: A total of 318 scans and 618 targets (314 primary targets and 304 nodal targets) met the inclusion criteria. Among the 618 targets, 85.4% were scored NI-RADS 1; 9.4% were scored NI-RADS 2; and 5.2% were scored NI-RADS 3. The rates of positive disease were 3.79%, 17.2%, and 59.4% for each NI-RADS category, respectively. Univariate association analysis demonstrated a strong association between the NI-RADS score and ultimate disease recurrence, with P < .001 for primary and regional sites. CONCLUSIONS: The baseline performance of NI-RADS was good, demonstrating significant discrimination among the categories 1-3 for predicting disease.

CT Accuracy of Extrinsic Tongue Muscle Invasion in Oral Cavity Cancer.

BACKGROUND AND PURPOSE: Extrinsic tongue muscle invasion in oral cavity cancer upstages the primary tumor to a T4a. Despite this American Joint Committee on Cancer staging criterion, no studies have investigated the accuracy or prognostic importance of radiologic extrinsic tongue muscle invasion, the feasibility of standardizing extrinsic tongue muscle invasion reporting, or the degree of agreement across different disciplines: radiology, surgery, and pathology. The purpose of this study was to assess the agreement among radiology, surgery, and pathology for extrinsic tongue muscle invasion and to determine the imaging features most predictive of extrinsic tongue muscle invasion with surgical/pathologic confirmation. MATERIALS AND METHODS: Thirty-three patients with untreated primary oral cavity cancer were included. Two head and neck radiologists, 3 otolaryngologists, and 1 pathologist prospectively evaluated extrinsic tongue muscle invasion. RESULTS: Fourteen of 33 patients had radiologic extrinsic tongue muscle invasion; however, only 8 extrinsic tongue muscle invasions were confirmed intraoperatively. Pathologists were unable to determine extrinsic tongue muscle invasion in post-formalin-fixed samples. Radiologic extrinsic tongue muscle invasion had 100% sensitivity, 76% specificity, 57% positive predictive value, and 100% negative predictive value with concurrent surgical-pathologic evaluation of extrinsic tongue muscle invasion as the criterion standard. On further evaluation, the imaging characteristic most consistent with surgical-pathologic evaluation positive for extrinsic tongue muscle invasion was masslike enhancement. CONCLUSIONS: Evaluation of extrinsic tongue muscle invasion is a subjective finding for all 3 disciplines. For radiology, masslike enhancement of extrinsic tongue muscle invasion most consistently corresponded to concurrent surgery/pathology evaluation positive for extrinsic tongue muscle invasion. Intraoperative surgical and pathologic evaluation should be encouraged to verify radiologic extrinsic tongue muscle invasion to minimize unnecessary upstaging. Because this process is not routine, imaging can add value by identifying those cases most suspicious for extrinsic tongue muscle invasion, thereby prompting this more detailed evaluation by surgeons and pathologists.

Preoperative therapy for esophageal cancer: a randomized comparison of chemotherapy versus radiation therapy.

Ninety-six patients with operable epidermoid cancer of the esophagus were entered into a phase III, random assignment study designed to compare the efficacy of two preoperative approaches (chemotherapy [CT] or radiation therapy [RT]). Major study end points were objective response rates, surgical outcome, and recurrence pattern. Patients were randomly assigned to receive either two cycles of cisplatin, vindesine, and bleomycin or 55 Gy of radiation before a planned surgical procedure. Postoperative crossover therapy (radiation to those receiving preoperative CT and vice versa) was given to patients with T3Nany or unresectable tumors. Objective response rates of the primary tumor to preoperative therapy were similar (RT 64%, CT 55%), as were operability rates (RT 77%, CT 75%), resection rates (RT 65%, CT 58%), and operative mortality (RT 13.5%, CT 11.1%). Significantly higher doses of CT could be administered when CT was given as initial therapy, rather than after RT/surgery. Local failure or persistence occurred in 33% of operable patients. The median survival for all patients was 11 months; 20% remain alive without disease (median follow-up, 34 months). Because of the crossover design, it was not possible to analyze survival according to the preoperative therapy arm alone. This study suggests that since CT is as effective in treating local tumor as RT, but can also potentially treat systemic disease, investigational programs using CT before surgery as part of initial treatment for localized esophageal cancer should continue. However, if a significant impact on overall survival is to be achieved, more effective chemotherapy regimens or schedules need to be identified. Outside of carefully designed clinical trials, surgery alone or radiation alone remain standard therapy.

Pilot trial of cisplatin, radiation, and WR2721 in carcinoma of the uterine cervix: a New York Gynecologic Oncology Group study.

PURPOSE: A phase I trial of WR2721 was initiated to determine the maximal safe dose for incorporation into a consecutive 5-day schedule of cisplatin administered concurrently with radiation therapy in patients with cervical cancer. PATIENTS AND METHODS: WR2721 was administered at 340 to 910 mg/m2/d immediately before cisplatin. Cisplatin was administered at 20 mg/m2/d for 5 days every 3 weeks in combination with external-beam radiation therapy and at 100 mg/m2 after each brachytherapy treatment. Pelvic radiation consisted of external-beam therapy to a dose of 39.6 Gy, followed by brachytherapy with cesium 137 tandem and ovoid insertions to deliver 80 Gy to point A and 55 Gy to point B. RESULTS: Twenty patients were enrolled; 19 were assessable. The dose-limiting toxicity of WR2721 was hypotension. No patients developed serious sequelae, but hypotension required a reduction in the dose of WR2721 at the highest dose level tested. The major grade 3 or 4 toxicities included transient azotemia (five of 19), leukopenia (nine of 19), vomiting (four of 19), and neurotoxicity (two of 19). One patient experienced an anaphylactic reaction to cisplatin. CONCLUSION: The recommended dose of WR2721 administered in conjunction with cisplatin on a daily x 5 schedule plus radiation therapy is 825 mg/m2/d for 5 days.

Management of hypocalcemic effects of WR2721 administered on a daily times five schedule with cisplatin and radiation therapy. The New York Gynecologic Oncology Group.

PURPOSE: To determine the effects of the chemoprotective agent, WR2721, administered on a daily x 5 schedule with cisplatin and radiation therapy, on calcium and parathyroid hormone (PTH) levels. PATIENTS AND METHODS: Twenty women with cervical cancer were enrolled in a clinical trial to determine the maximal safe dose of WR2721 plus radiation therapy and cisplatin on a novel daily x 5 schedule. Detailed studies of the effects of WR2721 on calcium and PTH levels were initiated after a patient developed symptomatic hypocalcemia. RESULTS: Treatment with WR2721 resulted in a rapid decline in serum PTH levels within 4 hours, which fell below the lower limits of normal at 24 hours, then returned to within normal limits at 48 hours. In contrast, serum levels of ionized calcium were not affected acutely, and declined by only 7% within 24 hours. However, this small decrease persisted for the 5 days of treatment. Hypocalcemic effects were successfully managed with oral calcium carbonate and calcitriol supplements. In one patient, particularly sensitive to the effects of WR2721, serum levels of ionized calcium decreased to less than 3.0 mg/dL despite oral calcium supplements. CONCLUSION: The effects of WR2721 on serum ionized calcium levels are mediated by direct inhibition of PTH activity; other effects such as inhibition of renal tubular calcium reabsorption cannot be excluded. We recommend that patients treated with WR2721, cisplatin, and radiation therapy receive routine oral calcium and calcitriol supplementation and that serum ionized calcium levels be monitored frequently.

Accuracy of Preoperative Imaging in Detecting Nodal Extracapsular Spread in Oral Cavity Squamous Cell Carcinoma.

BACKGROUND AND PURPOSE: The increasing impact of diagnosing extracapsular spread by using imaging, especially in patients with oropharyngeal squamous cell carcinoma, highlights the need to rigorously evaluate the diagnostic accuracy of imaging. Previous analysis suggested 62.5%-80.9% sensitivity and 60%-72.7% specificity. Our goals were to evaluate the accuracy of imaging in diagnosing extracapsular spread in a cohort of patients with oral cavity squamous cell carcinoma (pathologic confirmation of extracapsular spread routinely available), as a proxy for oropharyngeal squamous cell carcinoma, and to independently assess the reliability of imaging features (radiographic lymph node necrosis, irregular borders/stranding, gross invasion, and/or node size) in predicting pathologically proven extracapsular spread. MATERIALS AND METHODS: One hundred eleven consecutive patients with untreated oral cavity squamous cell carcinoma and available preoperative imaging and subsequent lymph node dissection were studied. Two neuroradiologists blinded to pathologically proven extracapsular spread status and previous radiology reports independently reviewed all images to evaluate the largest suspicious lymph node along the expected drainage pathway. Radiologic results were correlated with pathologic results from the neck dissections. RESULTS: Of 111 patients, 29 had radiographically determined extracapsular spread. Pathologic examination revealed that 28 of 111 (25%) had pathologically proven extracapsular spread. Imaging sensitivity and specificity for extracapsular spread were 68% and 88%, respectively. Radiographs were positive for lymph node necrosis in 84% of the patients in the pathology-proven extracapsular spread group and negative in only 7% of those in the pathologically proven extracapsular spread-negative group. On logistic regression analysis, necrosis (P = .001), irregular borders (P = .055), and gross invasion (P = .068) were independently correlated with pathologically proven extracapsular spread. CONCLUSIONS: Although the specificity of cross-sectional imaging for extracapsular spread was high, the sensitivity was low. Combined logistic regression analysis found that the presence of necrosis was the best radiologic predictor of pathologically proven extracapsular spread, and irregular borders and gross invasion were nearly independently significant.

The potential role of amifostine in conjunction with cisplatin in the treatment of locally advanced carcinoma of the cervix.

The treatment of locally advanced carcinoma of the cervix with radiation therapy as a single modality is inadequate, specifically for stage III and IVA disease. While chemotherapy as single-modality therapy is ineffective in advanced cervical cancer, there is some evidence of efficacy when used in combination with radiation therapy. A recently conducted phase II trial from the Albert Einstein College of Medicine used standard whole pelvic radiation therapy with concurrent cisplatin 20 mg/m(2)/d X 5 days for four courses in women with stage IB to IVA cervical cancer. Toxicities, mainly hematologic and soft tissue, were acceptable in this trial. There was only a modest impact on disease-free survival among women with stage III disease. A subsequent phase I trial conducted by the New York Gynecologic Oncology Group tested the addition of amifostine to the combination of cisplatin plus radiation therapy using the Albert Einstein College of Medicine regimen. Amifostine at doses escalated from 340 to 910 mg/m(2) was administered immediately before cisplatin. The dose-limiting toxicity was hypotension. Amifostine should be tested in future clinical trials either as a cytoprotective agent in patients receiving cisplatin plus radiation therapy or, alternatively, to assess dose intensification of cisplatin in combination with radiation therapy.

Methods of bolusing the tracheostomy stoma.

PURPOSE: The tracheostomy stoma is a potential site of recurrence for patients who have subglottic cancer or subglottic spread of cancer. In these patients, it is important that the anterior supraclavicular field does not underdose the posterior wall of the tracheostomy stoma when using a 6-MV anterior photon field. Conventionally, this problem is surmounted with placement of a plastic tracheostomy tube, which is uncomfortable for the patient, potentially traumatic, and can interfere with vocalization via a tracheal esophageal puncture. Our study was designed to investigate the dosimetry of this region and see if alternate methods would be effective. METHODS AND MATERIALS: A phantom was constructed using a No. 6 tracheostomy tube as the model for the tracheostomy curvature and size. Using the water-equivalent phantom, film dosimetry, and films oriented parallel to the en face field, we investigated the dose at the depth of the surface of the posterior wall of the phantom's tracheostomy stoma. Dose was measured both in space and at the tissue interface by scanning points of interest both horizontally and vertically. We measured doses with a No. 6 and No. 8 plastic tracheostomy tube, either 0.5 cm and 1.0 cm of bolus (1-cm airhole) with no tracheostomy tube, as well as 0.3 cm and 0.6 cm tissue-equivalent Aquaplast (Med-Tec Co., Orange City, Iowa) over the tracheostomy. Dosimetry at the posterior interface was confirmed using thermoluminescent dosimeters. RESULTS: Three mm and 6 mm of Aquaplast produced a posterior tracheal dose of 93% and 100%. CONCLUSION: There is no need for these patients to wear a temporary plastic tracheostomy tube during their external radiation therapy. Aquaplast should allow better position reproducibility, reduce trauma, not interfere with patient respiratory efforts, and be compatible with vocalization via a tracheal esophageal puncture.

Parotid gland tumors: a comparison of postoperative radiotherapy techniques using three dimensional (3D) dose distributions and dose-volume histograms (DVHS).

PURPOSE: To compare different treatment techniques for unilateral treatment of parotid gland tumors. METHODS AND MATERIALS: The CT-scans of a representative parotid patient were used. The field size was 9 x 11 cm, the separation was 15.5 cm, and the prescription depth was 4.5 cm. Using 3D dose distributions, tissue inhomogeneity corrections, scatter integration (for photons) and pencil beam (for electrons) algorithms and dose-volume histogram (DVH), nine treatment techniques were compared. [1] unilateral 6 MV photons [2] unilateral 12 MeV electrons [3] unilateral 16 MeV electrons [4] an ipsilateral wedge pair technique using 6 MV photons [5] a 3-field AP (wedged), PA (wedged) and lateral portal technique using 6 MV photons [6] a mixed beam technique using 6 MV photons and 12 MeV electrons (1:4 weighting) [7] a mixed beam technique using 6 MV photons and 16 MeV electrons (1:4 weighting) [8] a mixed beam technique using 18 MV photons and 20 MeV electrons (2:3 weighting) [9] a mixed beam technique using 18 MV photons and 20 MeV electrons (1:1 weighting). RESULTS: Using dose-volume histograms to evaluate the dose to the contralateral parotid gland, the percentage of contralateral parotid volume receiving > or = 30% of the prescribed dose was 100% for techniques [1], [8] and [9], and < 5% for techniques [2] through [7]. Evaluating the "hottest" 5 cc of the ipsilateral mandible and temporal lobes, the hot spots were: 152% and 150% for technique [2], 132% and 130% for technique [6]. Comparing the exit doses, techniques [1], [8] and [9] contributed to > or = 50% of the prescribed dose to the contralateral mandible and the temporal lobes. Only techniques [2] and [6] kept the highest point doses to both the brain stem and the spinal cord below 50% of the prescribed dose. CONCLUSION: The single photon lateral field [1] and the mixed electron-photon beams [8] and [9] are not recommended treatment techniques for unilateral parotid irradiation because of high doses delivered to the contralateral parotid gland and high exit doses which are associated with Xerostomia. The en face electron beam technique [2] and the mixed electron-photon beam technique [6] are unacceptable due to the excessive dose heterogeneity to the contiguous normal structures. In spite of optimal dose fall-off achieved using the en face technique [3], most patients cannot tolerate the resulting high skin doses. We conclude that the ipsilateral wedge pair [4], the 3-field [5], and the mixed electron-photon beam [7] techniques are optimal techniques in providing relatively homogeneous dose distributions within the target area and for minimizing dose to the relevant normal structures.

The relationship between dose heterogeneity ("hot" spots) and complications following high-dose rate brachytherapy.

PURPOSE: It is generally believed that "hot" spots should be avoided in radiotherapy because they lead to complications. Dose homogeneity within the target volume is much more difficult to achieve during brachytherapy than during external beam irradiation, and implants are rarely geometrically perfect. To not underdose some parts of the target volume, therefore, it may be necessary to accept hot spots in other parts of the target volumes, but it is not at all clear from the literature how much dose heterogeneity should be considered excessive. We undertook this study in an effort to determine just how high a dose to a hot spot is associated with clinically significant complications. METHODS AND MATERIALS: We studied 40 patients treated by high-dose rate brachytherapy with or without external irradiation. For each patient, we calculated the minimum dose to the "hottest" 1 cubic centimeter (cc) volume (Dmax1) and, for 18 patients, the minimum dose to the hottest 10 cc volume (Dmax10) as well. RESULTS: Considerable dose heterogeneity existed within the target volume. The Dmax1 ranged from 150-2000% (median 320%) of the minimum target dose (MTD). The median MTD/fraction was 2.50 Gy (range 1.50-25.00), and the median Dmax1/fraction was 10.00 Gy (range 3.75-150.00). The median Dmax1 from the entire course of brachytherapy was 75.00 Gy (range 25.00-550.00). Adding the doses from planned external irradiation, plus any prior irradiation to the same area, the median total Dmax1 was 112.50 Gy (range 30.00-580.00), yet the incidence of complications, even among those in the highest quartile of this dose range, was not greater than the lowest quartile. The total median Dmax10 was 85.00 Gy (range 32.00-130.00), but the incidence of complications was, again, similar whether the dose was in the lower or the upper half of this range (32.00-85.00 Gy, or 86.00-130.00 Gy, respectively). CONCLUSIONS: We had expected to find that the patients with the highest Dmax1 and/or Dmax10 would be the ones most likely to suffer complications, but the results did not support this hypothesis. Thus, dose heterogeneity, within the scope of our study, turned out to be rather unimportant with regard to complications. This finding contradicts the conventional wisdom and suggests that concerns about hot spots need not preclude optimization to ensure adequate dosage to all parts of the target volume.

Pelvic exenteration for cervix cancer: would additional intraoperative interstitial brachytherapy improve survival?

OBJECTIVE: Improved local control with the addition of brachytherapy to pelvic exenteration for recurrent cervical cancer has been reported to improve survival. We examined the sites of recurrence after pelvic exenteration to determine if these patients might have been salvaged by the improved local control promised by interstitial brachytherapy. We sought to identify risk factors available intraoperatively or perioperatively which might predict decreased local control. METHODS: A retrospective review of 26 patients with recurrent cervical cancer who underwent total pelvic exenteration since 1988 at our institution was performed. RESULTS: Overall, the mean follow-up was 29.5 months (range 6.1-81.6). Of the 26 patients, 14 had no evidence of disease (NED), 1 was alive with disease (AWD), 9 were dead of disease (DOD), and 2 died of unrelated causes (DOC). Seven of 26 patients (27%) had margins < or = 5 mm, of whom 2 were NED, 4 DOD, and 1 AWD. Seven of 26 (27%) patients had lymphovascular involvement (LVI) or perineural invasion (PNI) with clear margins. Three of the seven with LVI or PNI and clear margins were NED, and four DOD. Of the 10 failures, 9 (90%) had close margins, PNI, or LVI. CONCLUSION: Our data reveal that 9 of 14 (64%) patients with close margins, LVI, or PNI were DOD or AWD, and 6 of 9 of those patients suffered local regional failure alone. Brachytherapy has the potential to cure 6 of 14 (43%) patients with these risk factors. Further study of brachytherapy at the time of pelvic extenteration is warranted.

Postoperative radiotherapy with concurrent cisplatin appears to improve locoregional control of advanced, resectable head and neck cancers: RTOG 88-24.

PURPOSE: Despite aggressive surgery and postoperative radiation therapy, only 30% of patients who have advanced, potentially resectable carcinomas of the head and neck survive for 5 years. In the hope of improving this situation we studied the effect of postoperative radiotherapy delivered concurrently with cisplatin. METHODS AND MATERIALS: Patients who had Stage IV tumors and/or involved surgical margins received 60 Gy in 30 fractions over 6 weeks plus 100 mg/m2 of cisplatin on radiotherapy days 1, 23 and 43. Fifty-two patients participated in this trial and 51 were evaluated. Forty-three (84%) patients had pathologic T3 or T4 disease, 43 (84%) had Stage IV disease, and 27 (53%) had histologically involved surgical margins. RESULTS: Severe and life-threatening toxicities occurred in 20% and 12% of patients, respectively; the most common drug-related toxicities were leukopenia, anemia, nausea, and vomiting. Seventeen patients (43%) remain alive with no evidence of disease. Four patients (8%) died with no evidence of neoplastic disease, and one patient has died of a second independent malignancy. By actuarial analysis at 3 years, 48% of patients are alive, 81% have locoregional control of disease, and 57% are free of distant metastases. CONCLUSIONS: Based on comparison with similar patients treated in a prior Radiation Therapy Oncology Group/Intergroup trial (RTOG), we conclude that postoperative radiotherapy with concurrent cisplatin may improve locoregional control rates and should be prospectively tested.

Benign parotid hypertrophy on +HIV patients: limited late failures after external radiation.

PURPOSE: Although 8-10 Gy of external radiation therapy for +HIV associated parotid hypertrophy has achieved high response rates, the responses were transient with only 1/12 of patients retaining cosmetic control at median follow-up procedures of 9.5 months. Retreatment for failures after 8-10 Gy has also been unsatisfactory. Having shown that 24 Gy of external radiation therapy for benign parotid hypertrophy produced more durable cosmetic control than 8-10 Gy, we now report on longer follow-up periods on a group of patients receiving 24 Gy. MATERIALS AND METHODS: Twenty +HIV patients with clinical and radiographic evidence of lymphoepithelial lesions of the parotid were treated with 24 Gy of external radiation therapy using daily 1.5 Gy fractions; parallel opposed technique and 6 MV photons were used in 19 patients, and unilateral electron treatment was performed for one patient. RESULTS: With a mean follow-up period of 24 months, the cosmetic control appears durable. We have had no late failures past 24 months. Two patients have complained of modest xerostomia. There was no correlation with size of the cyst and eventual cosmetic result. CONCLUSIONS: Twenty-four Gy produces durable parotid control for HIV associated lymphoepithelial lesions of the parotid glands in +HIV patients. Failures after 2 years are uncommon and the side effects have been tolerable.

Randomized phase I/II trial of two variants of accelerated fractionated radiotherapy regimens for advanced head and neck cancer: results of RTOG 88-09.

PURPOSE: To establish the feasibility of performing split-course accelerated hyperfractionation (AHFX-S) and concomitant boost accelerated fractionation radiotherapy (AFX-C) for advanced head and neck cancer in a multi-institutional cooperative trial setting and to evaluate the tumor clearance rate and acute and late toxicity of these fractionation schedules. METHODS AND MATERIALS: Between February 1989 and January 1990, 75 patients with Stage III or IV squamous cell carcinoma of the head and neck were randomized to receive: (a) AHFX-S: 1.6 Gy/fraction, twice daily (6-h interval), 5 days/week, to a total dose of 67.2 Gy/42 fractions/6 weeks, with a 2-week rest after 38.4 Gy; or (b) AFX-C: 1.8 Gy/fraction/day, 5 daily fractions/week to 54 Gy/30 fractions/6 weeks to a large field and 1.5 Gy/fraction/day to a boost field, 6 h after large field treatment during the last 11 treatment days, to a total dose of 70.5 Gy/41 fractions/6 weeks. Acute and late toxicities were scored according to the RTOG normal tissue reaction scales and tumor clearance was evaluated at completion of therapy and at regular intervals thereafter. RESULTS: Of the 70 analyzable patients, 38 received AHFX-S and 32 received AFX-C. The two arms were balanced with respect to sex, age, T-stage, and Karnofsky Performance Status (KPS). However, the AHFX-S arm had a higher proportion of oropharyngeal primaries (63% vs. 44%), and Stage IV disease (82% vs. 50%) and lower proportion of oral cavity lesions (3% vs. 22%) and N0 disease (16% vs. 31%) than the AFX-C arm. The median follow-up was 2 years (range: 0.03-4.87 years). Tolerance of both variants of accelerated fractionated radiotherapy was satisfactory. There was no significant difference in local-regional control, disease-free survival, or survival between the two arms. The 2-year local-regional failure rate, survival, and disease-free survival was 50, 50, and 40%, respectively, for the entire group of patients. Acute radiation mucositis was increased in both arms. There was no significant difference in the incidence of grade 3 acute toxicities (63% vs. 56%) and grade 3 (14% vs. 14%) or grade 4 (6% vs. 17%) late toxicities. Permanent grade 4 late toxicity was observed in 6 and 7% of the patients, respectively. CONCLUSION: Results of this randomized Phase I/II trial showed that the two accelerated fractionated schedules studied can be successfully given in a multi-institutional cooperative trial. There was no significant difference in acute or late toxicities, local-regional control, disease-free survival, or survival in this small scale study. Therefore, a Phase III trial comparing the relative efficacy of these two accelerated fractionation schedules against standard fractionation and hyperfractionation has been activated.

Close or positive margins after surgical resection for the head and neck cancer patient: the addition of brachytherapy improves local control.

PURPOSE: Microscopically positive or close margins after surgical resection results in an approximately 21-26% local failure rate despite excellent postoperative external radiation therapy. We sought to demonstrate improved local control in head and neck cancer patients who had a resection with curative intent, and had unexpected, microscopically positive or close surgical margins. METHODS AND MATERIALS: Twenty-nine patients with microscopically close or positive margins after curative surgery were given definitive, adjuvant external radiation therapy and 125I brachytherapy. All 29 patients had squamous cell cancer and tonsil was the most common subsite within the head and neck region. After external radiation therapy and thorough discussions with the attending surgeon and pathologists, the slides, gross specimens, and appropriate radiographs were reviewed and a target volume was determined. The target volume was the region of the margin in question and varied in size based on the surgery and pathologic results. Once the target volume was identified the patient was taken back to the operating room for insertion of 125I seeds. Activity implanted (range 2.9-21.5 millicuries) was designed to administer a cumulative lifetime dose of 120-160 Gy. RESULTS: Twenty-nine patients were followed for a median of 26 months (range 5-86 months). Two-year actuarial local control was 92%. CONCLUSION: 125I, after external radiation therapy, is an excellent method to improve local control in the subset of patients with unexpectedly unsatisfactory margins.

Results of an RTOG phase III trial (RTOG 85-27) comparing radiotherapy plus etanidazole with radiotherapy alone for locally advanced head and neck carcinomas.

PURPOSE: The objectives of this study were to determine the efficacy and toxicity of Etanidazole (ETA), a hypoxic cell sensitizer, when combined with conventional radiotherapy (RT) in the management of advanced head and neck carcinomas. METHODS AND MATERIALS: From March 1988 to September 1991, 521 patients who had Stage III or IV head and neck carcinomas were randomized to receive conventional RT alone (66 Gy in 33 fractions to 74 Gy in 37 fractions, 5 fractions per week) or RT+ETA (2.0 g/m2 thrice weekly for 17 doses), of whom 504 were eligible and analyzable. Treatment assignments were stratified before randomization according to the primary site (oral cavity + hypopharynx vs. supraglottic larynx + oropharynx + nasopharynx), T-stage (T1-3 vs. T4), and N-stage (N0-2 vs. N3). Pretreatment characteristics were balanced. In the RT-alone arm, 39% of patients had T3 and 34% had T4 disease, whereas in the RT+ETA arm, 42% of patients had T3 and 33% had T4 disease. Thirty-eight percent of the RT-alone patients and 37% of the RT+ETA patients had N3 disease. The median follow-up of surviving patients was 3.38 years, with a range between 0.96 and 5.63 years. RESULTS: One hundred and ninety-four of the 252 (77%) RT+ETA patients received at least 14 doses of the drug. Overall RT protocol compliance rate was 82% in the RT-alone arm and 86% in the RT+ETA arm. No Grade 3 or 4 central nervous system or peripheral neuropathy was observed in the RT+ETA arm. Eighteen percent of the patients developed Grade 1 and 5% developed Grade 2 peripheral neuropathy. Other drug related toxicities included nausea/vomiting (27%), low blood counts (15%), and allergy (9%). Most of these toxicities were Grade 1 and 2. The incidence of severe acute and late radiation effects were similar between the two arms. The 2-year actuarial local-regional control rate (LCR) was 40% for the RT-alone arm and 40% for the RT+ETA arm. Two-year actuarial survival was 41% for the RT-alone arm and 43% for the RT+ETA arm (p = 0.65). Multivariate analyses were performed to investigate the influence of covariates on treatment effects. A strong treatment interaction with N-stage was revealed: LCR (50% vs. 40% at 2 years), RT+ETA improved for patients with N0-2 disease but not for N3 patients (22% for RT+ETA and 40% for RT). Further analyses showed that RT+ETA was more advantageous in N0-1 patients, with a 2-year LCR of 55% for RT+ETA vs. 37% for RT only (p = 0.03). A similar phenomenon was observed when using survival as the end point. CONCLUSION: The results showed that adding Etanidazole to conventional RT produced no global benefit for patients who had advanced head and neck carcinomas. There was a suggested benefit for patients who had N0-1 disease, and that needs to be confirmed by another study.