Adjuvant T-DM1 versus trastuzumab in patients with residual invasive disease after neoadjuvant therapy for HER2-positive breast cancer: subgroup analyses from KATHERINE.

BACKGROUND: In the KATHERINE study (NCT01772472), patients with residual invasive early breast cancer (EBC) after neoadjuvant chemotherapy (NACT) plus human epidermal growth factor receptor 2 (HER2)-targeted therapy had a 50% reduction in risk of recurrence or death with adjuvant trastuzumab emtansine (T-DM1) versus trastuzumab. Here, we present additional exploratory safety and efficacy analyses. PATIENTS AND METHODS: KATHERINE enrolled HER2-positive EBC patients with residual invasive disease in the breast/axilla at surgery after NACT containing a taxane (± anthracycline, ± platinum) and trastuzumab (± pertuzumab). Patients were randomized to adjuvant T-DM1 (n = 743) or trastuzumab (n = 743) for 14 cycles. The primary endpoint was invasive disease-free survival (IDFS). RESULTS: The incidence of peripheral neuropathy (PN) was similar regardless of neoadjuvant taxane type. Irrespective of treatment arm, baseline PN was associated with longer PN duration (median, 105-109 days longer) and lower resolution rate (∼65% versus ∼82%). Prior platinum therapy was associated with more grade 3-4 thrombocytopenia in the T-DM1 arm (13.5% versus 3.8%), but there was no grade ≥3 hemorrhage in these patients. Risk of recurrence or death was decreased with T-DM1 versus trastuzumab in patients who received anthracycline-based NACT [hazard ratio (HR) = 0.51; 95% confidence interval (CI): 0.38-0.67], non-anthracycline-based NACT (HR = 0.43; 95% CI: 0.22-0.82), presented with cT1, cN0 tumors (0 versus 6 IDFS events), or had particularly high-risk tumors (HRs ranged from 0.43 to 0.72). The central nervous system (CNS) was more often the site of first recurrence in the T-DM1 arm (5.9% versus 4.3%), but T-DM1 was not associated with a difference in overall risk of CNS recurrence. CONCLUSIONS: T-DM1 provides clinical benefit across patient subgroups, including small tumors and particularly high-risk tumors and does not increase the overall risk of CNS recurrence. NACT type had a minimal impact on safety.

The duration of fibre-optic intubation is increased by cricoid pressure. A randomised double-blind study.

BACKGROUND: In some categories of patients, a rapid sequence induction using a fibre-optic method may be indicated. The aim of the present study was to examine the effect of cricoid pressure (CP) on the duration of fibre-optic intubation. The hypothesis was that CP would prolong the intubation time. METHODS: The study was a randomised, double-blind, cross-over study. The patients were intubated twice, in a randomised way, using a flexible fibrescope once with and once without CP. The intubation time and the visualisation of the glottis were registered. If the intubation was not completed within 180 s, it was registered as failed. CP was standardised to a pressure of 30 N. The data are given as the mean (standard deviation) or median [interquartile] (range). RESULTS: Fifty patients were included, with a mean age of 53 years (14.6) and mean body mass index of 26.4 (4.3). Three intubations without and 13 intubations with CP failed. The durations of intubation without and with CP were 59 s [53-79 s] (34-144 s) and 75 s [67-104 s] (43-179 s), respectively (P < 0.001). CONCLUSION: The study showed that CP prolongs the duration of fibre-optic intubation in patients with Mallampati grades 1-2.

Is diagnostic review of radiotherapy-planning CT scans important in the conformal therapy era?

OBJECTIVE: Detailed CT scans are often acquired during the radiotherapy planning process. This study was performed to determine the incidence of important benign and cancer-related CT findings on these scans. SUBJECTS AND METHODS: From December 1998 to December 2000, 162 radiotherapy patients who were to be treated curatively underwent treatment planning CT scans on a helical scanner in the radiology department at Washington Hospital, Fremont, CA. All CT scans were prospectively interpreted relative to diagnoses, and reports were dictated for the medical records. The diagnostic reports and records on all patients were reviewed to determine the incidence of previously unknown benign or cancer-related findings, the impacts of such findings on treatment, and the need for additional radiologic studies or procedures on the basis of the CT interpretations. RESULTS: Incidental benign findings were noted for 32 patients (20%). Potentially important benign findings were noted for three patients: two with aneurysms and one with a possible deep vein thrombosis. Potentially cancer-related findings were reported in 20 patients: a single liver lesion (four patients), multiple liver lesions (two patients), possible or probable lymphadenopathy (11 patients), abnormal soft tissue (one patient), a small-bowel obstruction (one patient), and a breast mass (one patient). After reviewing prior diagnostic studies and obtaining additional recommended studies, the physicians found that only three of the previously unknown findings required further investigation: two aneurysms, which did not require near-term treatment, and one metastatic neck node. CONCLUSION: Routine diagnostic interpretation of radiotherapy planning scans resulted in few important medical findings and changed patient care for less than 1% of the patients.

Breast electron boost planning: comparison of CT and US.

PURPOSE: To compare computed tomography (CT) with ultrasonography (US) for depiction of the biopsy cavity. MATERIALS AND METHODS: Thirty-two consecutive patients who underwent radiation therapy following lumpectomy with a planned electron boost were examined. At the time of simulation for whole-breast radiation therapy, all patients underwent planning CT (CT 1) at 3-mm section intervals. At the time of electron boost simulation, US was performed to define the biopsy cavity. In 17 cases, a second CT examination (CT 2) was performed at the time of electron boost simulation. CT and US studies were reviewed jointly and assigned a cavity visualization score (CVS) of 1 (cavity not visualized) to 5 (all cavity margins clearly defined). RESULTS: The median CVS at CT 1 was 5; at CT 2, 4; and at US, 4. For patients who underwent all three studies, the median CVS at CT 1 was 5; at CT 2, 4; and at US, 4. Factors related to CVS at CT 1 were homogeneous versus heterogeneous appearance (score, 5 vs 4), surgery-to-CT interval (< or =30 days, 5; 31-60 days, 4; >60 days, 4), and cavity size (>15 cm(3), 5; <15 cm(3), 4). In all cases, cavity volume decreased somewhat during the CT 1-to-CT 2 interval. CONCLUSION: CT performed at the time of whole-breast simulation can be used to plan electron boost fields, with cavity visualization similar to that at US.

Treatment results of carcinoma in situ of the glottis: an analysis of 82 cases.

OBJECTIVES: To evaluate the results of different treatment modalities for carcinoma in situ of the glottis, and to identify important prognostic factors for outcome. DESIGN: Review of 82 cases treated definitively for glottic carcinoma in situ between 1958 and 1998. The median follow-up for all patients was 112 months, and 90% had more than 2 years of follow-up. SETTING: Academic tertiary care referral centers. INTERVENTION: Fifteen patients were treated with vocal cord stripping (group 1), 13 with more extensive surgery (group 2) including endoscopic laser resection (11 patients) and hemilaryngectomy (2 patients), and 54 with radiotherapy (group 3). Thirty patients had anterior commissure involvement and 9 had bilateral vocal cord involvement. Radiotherapy was delivered via opposed lateral fields at 1.5 to 2.4 Gy per fraction per day (median fraction size, 2 Gy), 5 days per week. The median total dose was 64 Gy, and the median overall time was 47 days. MAIN OUTCOME MEASURES: Initial locoregional control (LRC), ultimate LRC, and larynx preservation. RESULTS: The 10-year initial LRC rates were 56% for group 1, 71% for group 2, and 79% for group 3. Of those who failed, the median time to relapse was 11 months for group 1, 17 months for group 2, and 41 months for group 3. Univariate analysis showed that the difference in initial LRC rates between groups 1 and 3 was statistically significant (P =.02), although it was not statistically significant on multivariate analysis (P =.07). Anterior commissure involvement was an important prognostic factor for LRC on both univariate (P =.03) and multivariate (P =.04; hazard ratio, 1.6) analysis, and its influence appeared to be mainly confined to the surgically treated patients (groups 1 and 2). The 10-year larynx preservation rates were 92% for group 1, 70% for group 2, and 85% for group 3. Anterior commissure involvement was the only important prognostic factor for larynx preservation (P =. 01) on univariate analysis. All but 2 patients in whom treatment failed underwent successful salvage surgery. Voice quality was deemed good to excellent in 73% of the patients in group 1, 40% in group 2, and 68% in group 3. CONCLUSIONS: Treatment of carcinoma in situ of the glottis with vocal cord stripping or more extensive surgery or radiotherapy provided excellent ultimate LRC and comparable larynx preservation rates. Anterior commissure involvement was associated with poorer initial LRC and larynx preservation, particularly in the surgically treated patients. The choice of initial treatment should be individualized, depending on patient age, reliability, and tumor extent. Pretreatment and posttreatment objective evaluation of voice quality should be helpful in determining the best therapy for these patients.

Radiation therapy for benign disease of the orbit.

Benign diseases of the orbit can cause significant impairment of visual function through direct effects on the eye or supporting orbital tissues. Persistent moderate-to-severe inflammatory symptoms, diplopia, and visual loss may prompt therapeutic intervention. Low doses of external-beam irradiation (20 Gy in 2-Gy fractions) have an efficacy equivalent to corticosteroid medications in the treatment of both Graves' ophthalmopathy and orbital pseudotumor, with response rates of 50% to 80%. Appropriate patient selection, coordination with other medical subspecialties, and careful treatment planning are important in maximizing benefit from radiation therapy. In the case of Graves' ophthalmopathy, quantitative assessment of orbital disease severity and thyroid status as well as attainment of cross-sectional imaging should be performed before treatment. Patients whose thyroid disease is controlled but who have moderate-to-severe active orbital involvement can be offered orbital radiation therapy with a high likelihood of response. Stability of disease is generally obtained within 6 months; surgical correction of residual abnormalities may be required. For orbital pseudotumor, attainment of histological material before treatment is important in excluding benign or malignant systemic diseases, including malignant lymphoma. Genotypic abnormalities may exist in patients with reactive lymphoid hyperplasia, some of whom ultimately develop systemic lymphoma. Within the dose range recommended for treatment of Graves' ophthalmopathy and pseudotumor, late radiation effects on the retina or optic nerve should be nonexistent. Adequate lens shielding is required, however, to prevent cataract formation. This may require individualized treatment planning with computed tomography at the time of simulation. Pterygia recurrence after bare sclera excision occurs in at least 30% of cases, usually within 6 months of surgery. Radiation of the surgical bed using a strontium-90 source, beginning within 24 hours postoperatively, reduces the risk of recurrence substantially. Late scleral complications have been associated with large single-fraction treatments. To achieve maximal efficacy with minimal complications, fractionated treatment should be given by radiation oncologists experienced with the technique using sources calibrated by the National Bureau of Standards.

Results of the 1988-1989 Patterns of Care Study process survey for Hodgkin's disease.

PURPOSE: To document national standards of care for patients receiving radiotherapy as part of curative treatment for Hodgkin's disease. MATERIALS AND METHODS: A national survey was conducted of 61 institutions treating 275 patients with Stages I-III Hodgkin's disease and representing six facility type strata. Pretreatment evaluation, radiotherapy treatment parameters, and use of combined modality therapy were assessed. RESULTS: Ann Arbor stage for the 275 patients was as follows: IA, 69 (25%); IB, 7 (3%); IIA, 123 (45%); IIB, 36 (13%); IIIA 23 (8%), IIIB, 14 (5%); unknown, 3 (1%). Pretreatment evaluation included complete blood count for 93%, sedimentation rate in 29%, chest CT in 88%, abdominal CT scan in 87%, and bone marrow biopsy in 81%. Lymphangiograms were obtained in 50% of cases; laparotomy was performed in 46%. The yield of positive findings in the spleen at laparotomy was 6.5 % overall. Facility differences with respect to staging were seen only for the use of gallium scans, which were more commonly used in academic centers (44% vs. 15-23% elsewhere, p<0.001). Radiotherapy was delivered with a linear accelerator in 94% of cases. Treatment simulation was performed for 94% and individualized blocks constructed for 95% overall; however, freestanding facilities had a lower rate of performance of these procedures (78% vs. 98-99% for simulation and 88% vs. 96-99% for customized blocking, p<0.001). The mean supradiaphragmatic dose was 36.74 Gy and the mean subdiaphragmatic dose was 33.81 Gy. Planned combined modality therapy was given in 36% of patients. The use of combined modality therapy by stage was as follows: IA, 11%; IB, 43%; IIA, 30%; IIB, 68%; IIIA, 57%; IIIB, 100%. Chemotherapy was completed prior to radiation in 80% of cases and generally consisted of ABVD (32%), an alternating regimen (25%), or MOPP (22%). Among Stage I/II patients, use of chemotherapy was associated with reduced radiation doses (mean supradiaphragmatic dose 34.53 Gy vs. 38.43 Gy and mean subdiaphragmatic dose 31.27 Gy vs. 34.51 Gy), and reduced volumes of treatment (87% vs. 28% treated to one side of the diaphragm only). Laparotomy was not associated with decreased supra- or subdiaphragmatic radiation doses or decreased volumes of treatment. CONCLUSIONS: With the exception of gallium scans, pretreatment evaluation is relatively uniform across facility strata. Increased understanding of prognostic factors in Hodgkin's disease and greater use of planned combined modality therapy for higher risk patients appears to have contributed to a decreased use of and low yield of positive findings for laparotomy. Laparotomy was not associated with reduced radiation volumes or doses. Freestanding radiation facilities had a lower rate than other facility types for the performance of treatment simulation and customized patient blocking.

Utility of three-dimensional planning for axillary node coverage with breast-conserving radiation therapy: early experience.

PURPOSE: To examine the dosimetric axillary nodal coverage with standard tangential breast radiation fields and determine the utility of three-dimensional treatment planning for such coverage. MATERIALS AND METHODS: Six consecutive patients who were to undergo whole-breast irradiation underwent computed tomographic scanning with 5-mm sections at the time of treatment simulation. Contours were made with a commercial workstation for the lower axillary tissues, lungs, and heart. Axillary coverage was examined with three-dimensional isodose visualization and dose-volume histograms for four plans for each patient: (a) standard tangential radiation fields designed to cover only the breast, with clinical setup; (b) standard tangential fields with beam's-eye-view optimization of collimator angles for axillary and breast coverage; (c) standard tangential fields with adjustment of field width and collimator angles; and (d) customized fields, by adjusting width, collimator angle, and gantry angle and by using customized blocks. RESULTS: With plan a, only one patient had a simulated mean axillary dose greater than 90% of that prescribed. Underdosing occurred primarily in the posterior-superior axillary nodal region. Plan b improved axillary coverage; five patients had a simulated mean axillary dose of 89% or more of the prescribed dose, with adequate whole-breast coverage and no increased pulmonary or cardiac doses. Adjusting the field width and gantry angle further improved simulated mean axillary doses; however, customized blocking was then required to avoid increased mean pulmonary and cardiac doses and unacceptable contralateral breast doses. CONCLUSION: When coverage of lower axillary nodal tissue is desired at breast irradiation, three-dimensional planning with beam's-eye-view adjustment of tangential fields should be considered.

The advantages of three-dimensional conformal radiotherapy for treatment of childhood cancer.

Three-dimensional treatment planning with delivery of conformal radiotherapy has been demonstrated to improve tumor targeting and to reduce normal tissue volume exposed in several studies of malignancies in adults. Furthermore, institutional clinical protocols have accomplished escalation of radiation dose with enhanced treatment efficacy and stable to decreased late effects in patients with prostate carcinoma. In the treatment of malignancies in children, there are several aspects of therapy which may be particularly amenable to improvement with three-dimensional treatment planning. First, the occurrence of large, irregular tumor volumes close to critical normal structures is common in solid tumors in children. The acquisition of detailed computerized tomography (CT) images at the time of simulation, along with the use of three-dimensional reconstruction and beam's-eye-view capabilities, should greatly improve tumor targeting and allow more selective blocking of normal structures. In addition, the enhanced sensitivity of developing organs and tissues to radiation in combination with high expectations for overall survival with current treatment programs has resulted in greater awareness of the late effects of treatment. Today, the goal of pediatric radiotherapy is to provide high rates of local tumor control without significant late effects, such as impairment of growth and development and injury to organ function. The use of conformal radiotherapy is likely to be an important advance in realizing this goal. The ability to use novel beam arrangements and to evaluate radiotherapy treatment plans with quantitative tools, such as dose-volume histogram analysis or probabilities of normal tissue complications, should enable the use of treatment programs with a lessened risk of late effects. However, the rarity of pediatric tumors is unlikely to permit a controlled trial of conformal compared to conventional therapy. In this article, we use three case illustrations to demonstrate and discuss the potential advantages of conformal radiotherapy in the treatment of childhood cancer.

Women's use of resources in decision-making for early-stage breast cancer: results of a community-based survey.

BACKGROUND: The majority of women with stage I/II breast cancer may choose between mastectomy and breast-conserving therapy (BCT). A survey was designed to examine the resources women used in making this decision. METHODS: From 1990 to 1994, 261 patients were diagnosed with or treated for stage I/II breast cancer at Washington Hospital (Fremont, CA). One-hundred seventy-six surviving patients received a questionnaire asking them to anonymously rank various medical and nonmedical persons, audio and visual materials, and decision criteria on a 5-point scale with regard to their influence on that individual's choice to undergo BCT or mastectomy. The BCT and mastectomy groups were similar demographically; approximately 50% were college-educated. Statistical significance of the difference in means between groups was assessed with the t test. The response rate to the survey was 65%. RESULTS: The average survey ranking was > 1.0 for the following: surgeon (4.5), primary care physician (2.8), spouse (2.4), radiation oncologist (1.7), medical oncologist (1.5), American Cancer Society brochure (1.4), and children (1.2). The ranking of children (p = 0.08), friends (p = 0.08), parents (p = 0.09), and spouse (p = 0.13) was higher in the mastectomy group; the ranking of the radiation oncologist (p = 0.001) and ACS brochure (p = 0.03) was higher in the BCT group. The majority of patients consulted only with the surgeon (96%), primary care physician (64%), and spouse (55% overall, 75% among married patients) before making a treatment choice. Decision criteria were ranked as follows: chance for cure (4.5), physician recommendation (3.7), potential side effects (1.7), cosmetic appearance (1.3), sexual attractiveness (1.1), treatment convenience (1.0), and desire to avoid mastectomy (1.5). Desire to avoid mastectomy was higher in the BCT group (p < 0.0001); ranking of chance for cure was higher in the mastectomy group (p = 0.12). Overall satisfaction was higher in the BCT group; 87% of these patients were "very satisfied" with their decision versus 68% for the mastectomy group (p = 0.005). Review of the admitting records for 125 patients treated with mastectomy indicated that 46% had clear medical or personal contra-indications to BCT, but that the remainder might have benefitted from specialty consultation. CONCLUSIONS: The surgeon's recommendation and the patient's perception of chance for cure were the most influential factors affecting treatment decision. There was a limited use of specialty consultation or written and audiovisual materials in this educated patient population. The survey results suggest potential areas of intervention to improve rates of BCT, namely use of up-front multidisciplinary evaluation, further education of primary care physicians, and greater attention to concerns of family members.

Breast-conserving radiation therapy: potential of inverse planning with intensity modulation.

PURPOSE: To evaluate inverse planning with beam-intensity modulation in breast-conserving radiation therapy. MATERIALS AND METHODS: A prototype inverse treatment-planning system was used in five patients with early-stage breast tumors. The prescription for the breast was 5,040 cGy in 180-cGy fractions, with the primary tumor site receiving 6,000 cGy in 214-cGy fractions. Isodose distributions from the prototype were compared section by section with those from conventional three-dimensional planning. RESULTS: The inverse planning system showed dose variation of 84%-98% to 111%-113% in the primary tumor site. For whole-breast irradiation, 95% of the target volume received at least 4,000 cGy. High-dose areas were adjacent to the primary site. Lower-dose areas were in the most medial part of the breast. Compared with the conventional system, target doses were similar. The volume of lung and heart that received high doses was smaller; however, larger lung and heart volumes received doses of less than 1,200 cGy. CONCLUSION: Intensity modulation may accomplish "concomitant boost" treatment. Acceptable dose gradients are achieved in the target volumes, with lower volumes of high-dose treatment in normal tissue. Plans that required comprehensive nodal radiation, in particular, were improved relative to conventional plans. Optimization of the planning system is needed to minimize the lung and heart volumes that receive low-dose radiation.

The results of radical prostatectomy at a community hospital during the prostate specific antigen era.

BACKGROUND: The use of radical prostatectomy in the treatment of prostate cancer has increased with the advent of prostate specific antigen (PSA) screening. Few series have examined the relapse rates after prostatectomy relative to pre-treatment prognostic factors, such as preoperative PSA and Gleason scores. The characteristics and outcome of patients diagnosed with prostate cancer and treated with radical prostatectomy at community hospitals in the prostate specific antigen era have not been described in detail. METHODS: The tumor registry records were obtained for all patients diagnosed with prostate cancer and treated with radical prostatectomy at Washington Hospital, Fremont, CA, from 1990 through 1993. The clinical and pathologic characteristics, including the original pathology report, for the 100 patients were reviewed by a single physician. Relapse was defined by the persistence or appearance of a PSA value greater than 0.2 ng/mL (Hybritech, Inc., San Diego, CA) following surgery or by clinical evidence of recurrent disease. Crude and actuarial probabilities of relapse were analyzed relative to pre-treatment PSA values, Gleason score, pathologic stage, and surgical margin status. The median follow-up time was 2.5 years. RESULTS: The pT-classification distribution of the 100 cases was as follows: T1, 4%; T2A, 14%; T2B, 11%; T2C, 49%; T3A, 8%; T3B, 2%; T3C, 6%; and N+, 6%. Pretreatment PSA values were less than or equal to 4 ng/mL for 10 patients, greater than 4 to 10 ng/mL for 38 patients, greater than 10 to 20 ng/mL for 27 patients, and greater than 20 ng/mL for 13 patients. The value was unknown for 12 patients. The Gleason score was less than or equal to 5 for 40%, 6 for 17%, 7 for 31%, and 8 to 10 for 12%. Positive surgical margins were noted in 30% of the patients. The actuarial probability of overall survival and freedom from relapse for the entire group of patients at 3 years was 95% and 73%, respectively. Pre-treatment PSA values greater than 20 ng/mL, Gleason score greater than or equal to 7, and pT3 classification were significant predictors of relapse in univariate analysis. Preoperative PSA greater than 20 ng/mL and Gleason score were significant prognostic factors in multivariate analysis. Pathologic margin status was not a significant predictor of relapse in this experience. CONCLUSIONS: Short-term relapse rates are high among those patients with preoperative PSA values greater then 20 ng/mL or Gleason scores greater than or equal to 7. Overall results of radical prostatectomy at this community hospital were similar to those reported at referral centers.

The importance of the lumpectomy surgical margin status in long-term results of breast conservation.

BACKGROUND: The impact of the surgical margin status on long-term local control rates for breast cancer in women treated with lumpectomy and radiation therapy is unclear. METHODS: The records of 289 women with 303 invasive breast cancers who were treated with lumpectomy and radiation therapy from 1972 to 1992 were reviewed. The surgical margin was classified as positive (transecting the inked margin), close (less than or equal to 2 mm from the margin), negative, or indeterminate, based on the initial biopsy findings and reexcision specimens, as appropriate. Various clinical and pathologic factors were analyzed as potential prognostic factors for local recurrence in addition to the margin status, including T classification, N classification, age, histologic features, and use of adjuvant therapy. The mean follow-up was 6.25 years. RESULTS: The actuarial probability of freedom from local recurrence for the entire group of patients at 5 and 10 years was 94% and 87%, respectively. The actuarial probability of local control at 10 years was 98% for those patients with negative surgical margins versus 82% for all others (P = 0.007). The local control rate at 10 years was 97% for patients who underwent reexcision and 84% for those who did not. Reexcision appears to convey a local control benefit for those patients with close, indeterminate, or positive initial margins, when negative final margins are attained (P = 0.0001). Final margin status was the most significant determinant of local recurrence rates in univariate analysis. By multivariate analysis, the final margin status and use of adjuvant chemotherapy were significant prognostic factors. CONCLUSIONS: The attainment of negative surgical margins, initially or at the time of reexcision, is the most significant predictor of local control after breast-conserving treatment with lumpectomy and radiation therapy.

Radiotherapy for carcinoma-in-situ of the glottic larynx.

PURPOSE: To describe the long-term results of radiotherapy as treatment for carcinoma-in-situ of the glottic larynx. METHODS AND MATERIALS: Twenty-nine patients with a histologic diagnosis of carcinoma-in-situ (CIS) of the true vocal cord were treated in the Department of Radiation Oncology at Stanford University Medical Center over a 32-year period from 1958-1990. Twenty patients were treated at the time of initial diagnosis following biopsy only (12) or vocal cord stripping (8) and the remainder were referred for treatment of recurrent CIS following one or more prior surgical procedures. Treatment was delivered with megavoltage equipment to a total dose of 53-66.5 Gy (mean 62 Gy) in 180-250 cGy fractions. The mean follow-up time is 10 years, with a range of 2-27 years. RESULTS: Two patients relapsed locally. One patient had recurrent CIS 5 months after radiotherapy and was salvaged with vocal cord stripping. The other developed microinvasive squamous cell carcinoma and underwent total laryngectomy. The actuarial freedom from local relapse and overall survival at 10 years are 92% and 64%, respectively. No local failures occurred more than 5 years after treatment. Late complications from radiotherapy were rare, and voice quality was good-to-excellent in 90% of patients. The actuarial risk of a second aerodigestive tract malignancy is 11% at 10 years. CONCLUSION: Radiation therapy is an effective and safe treatment modality for carcinoma-in-situ of the glottic larynx. Long-term local control is achieved in approximately 90% of patients with 75% having normal voice.

Radiotherapy is successful treatment for orbital lymphoma.

PURPOSE: To describe the clinical presentation, treatment technique, outcome and complications in a large single institutional experience using radiotherapy for treatment of orbital lymphoma. METHODS AND MATERIALS: Twenty-five patients with lymphoma of the orbit or ocular adnexa were treated with radiotherapy at Stanford University Medical Center during the fourteen year period, 1977-1991. Patients were staged using the Ann Arbor criteria with chest x-ray, computerized tomography of abdomen and orbits, lymphangiogram, and bone marrow biopsy. Patients with disease localized to the orbits as well as those with disseminated disease and symptomatic orbital lesions were treated. Thirty-one involved eyes were treated. Mean radiotherapy dose was 35.3 Gy, with a range of 28 Gy to 40.2 Gy. Lens protection was used in all cases. Two patients with diffuse large cell lymphoma also received chemotherapy as part of their initial treatment. Follow-up ranged from 10 months to 13 years, with a mean follow-up time of 4 years. RESULTS: Twenty patients had disease confined to one or both orbits (Stage I). One patient had a monoclonal atypical infiltrate, while the remainder had a histologic diagnosis of malignant lymphoma: diffuse small lymphocytic, 13; follicular mixed, 3; diffuse small cleaved, 3; diffuse large cell, 2; follicular small cleaved, 1; follicular and diffuse small cleaved, 1; undifferentiated, 1. Two local relapses occurred; the actuarial 5-year freedom from local relapse is 89%. Actuarial 5-year freedom from distant relapse, freedom from any relapse and overall survival are 77%, 70%, and 93%, respectively. Acute complications of treatment were mild. Late complications included transient cystoid macular edema (one patient), asymptomatic subcapsular and medial sector cataract formation (two patients), retinopathy (two patients), mild eyelid retraction (one patient), and dry eye with secondary conjunctivitis (one patient). CONCLUSION: Carefully planned radiotherapy with lens shielding is an effective and safe treatment in the management of orbital lymphoma. We recommend megavoltage radiation doses of 30-35 Gy in 180-200 cGy fractions for low grade lesions, and 36-40 Gy for intermediate and high grade lesions.