Oral tongue cancer in patients less than 45 years old: institutional experience and comparison with older patients.

PURPOSE: To evaluate the demographics, differential risk profile, and treatment outcome in patients with squamous cell carcinomas (SCCs) of the oral tongue according to age at diagnosis. PATIENTS AND METHODS: Patients with invasive SCC of the oral tongue who presented during the years 1985 to 1996 were identified using institutional tumor registry data. Demographics and clinical and pathologic characteristics were abstracted from the medical charts. RESULTS: Eighty-eight patients were identified; 87 were included for analysis. Thirty patients were diagnosed at < or = 45 years of age and 57 at > or = 46 years. The groups showed comparable American Joint Committee on Cancer (AJCC) staging and male predominance. Prior exposure to tobacco and/or alcohol was noted in 40% and 82% of younger and older patients, respectively (P < .001); multiple smoking-related cancers occurred only in older patients (24.5% of older patients, P < .001). With median follow-up time of 29 months (younger group) and 21 months (older group), there were no significant differences in relapse rates, cancer-free survival (CFS), and overall survival (OS) rates (actuarial 5-year CFS rate, 48% and 54% in the younger and older patients, respectively; P = .91). Grouping patients according to smoking and/or alcohol history showed a trend toward better CFS in those with prior exposure to tobacco or alcohol compared with those with neither (5-year CFS rate, 60% and 38%, respectively, P = .11). In a multivariate analysis of all patients, with age used as a continuous parameter, only stage predicted CFS (P = .0019); for patients treated surgically with curative intent, only risk group predicted CFS (P = .0369). CONCLUSION: Prognosis of oral tongue SCC was not affected by age at diagnosis. CFS rates tended to be worse in cases not related to prior tobacco or alcohol exposure. Multiple smoking-related cancers occurred only in older patients.

Pretreatment hemoglobin level influences local control and survival of T1-T2 squamous cell carcinomas of the glottic larynx.

PURPOSE: A number of reports have documented the relationship between pretreatment hemoglobin level and local control and/or survival in the treatment of cervix, bladder, and advanced head and neck tumors. Consideration of correcting anemia before initiation of radiation therapy may prove increasingly important as clinical trials use intensive induction chemotherapy in the treatment of head and neck carcinomas. Neoadjuvant chemotherapy may produce anemia, which in turn may reduce the effectiveness of subsequent irradiation. MATERIALS AND METHODS: One hundred nine patients with T1-2N0 squamous cell carcinoma of the glottic larynx were treated with definitive radiotherapy at the Fox Chase Cancer Center between June 1980 and November 1990. Follow-up times ranged from 26 to 165 months (median, 82). RESULTS: The 2-year local control rate for patients who presented with a hemoglobin level < or = 13 g/dL was 66%, compared with 95% for patients with a hemoglobin level more than 13 g/dL (P = .0018). The 2-year survival rate for patients with a hemoglobin level < or = 13 g/dL was 46%, compared with 88% for patients with a hemoglobin level more than 13 g/dL (P < .001). Cox proportional hazards regression analysis showed that hemoglobin level (P = .0016) was the only variable that significantly influenced local control (P = .0016) and survival (P < .0001). CONCLUSION: Patients who presented with hemoglobin levels more than 13 g/dL had significantly higher local control and survival rates. The strong apparent correlation between hemoglobin level, local control, and survival supports consideration of correcting anemia before initiation of radiation therapy.

T1-T2 squamous cell carcinoma of the glottic larynx treated with radiotherapy: a multivariate analysis of variables potentially influencing local control.

PURPOSE: To examine various parameters that might influence the probability of local control of T1-T2 glottic carcinoma treated with radiotherapy. METHODS AND MATERIALS: Two hundred forty-seven patients with invasive, previously untreated T1-T2 squamous cell carcinoma of the glottic larynx were treated with radiotherapy between May 1977 and December 1989. All patients had a minimum 2-year follow-up. To minimize treatment-related variables, only patients with T1 lesions treated once daily at 225 cGy per fraction and patients with T2 lesions treated once daily at 225 cGy per fraction or twice daily at 120 cGy per fraction were included. Surgical alternative, thickness of the neck at the posterior edge of the lateral fields, vocal cord mobility, anterior commissure involvement, gender, and T stage were evaluated in a multivariate analysis. RESULTS: The 5-year local control rates, calculated by the product-limit method, were T1a, 95%; T1b, 96%; T2a, 87%; and T2b, 76%. The 5-year local control rate for patients with T2 lesions treated with once-daily fractionation was 81% compared with 91% for those who received twice-a-day radiotherapy. For the endpoint of local control with irradiation, the surgical alternative (p = .020) and cord mobility (p = .001) were of independent prognostic significance. CONCLUSION: Of the variables analyzed, only vocal cord mobility and surgical alternative significantly influenced local control. Specifically, anterior commissure involvement and neck thickness did not affect local control.

Intra- and interfractional reproducibility of tangential breast fields: a prospective on-line portal imaging study.

PURPOSE: A perception exists that weekly verification films accurately reflect the setup of the tangential breast portals. This prospective study was undertaken to assess patient movement during treatment and setup reproducibility of tangential breast fields using electronic on-line portal imaging. METHODS AND MATERIALS: Thirteen patients with carcinoma of the breast were treated on a linear accelerator equipped with an on-line portal imaging system. Patients were immobilized daily with an alpha cradle. The medial and lateral tangential fields were imaged and 139 fractions, 225 portal fields, and 4450 images were obtained. Images were then analyzed off line and 22,250 measurements were made from these images. Anatomical features recorded include the lung area (LA), central lung distance (CLD), central breast distance (CBD), central flash distance (CFD), and inferior central margin (ICM). Intrafractional variations were calculated for every portal field and fraction for each patient. Interfractional variations were determined by finding the variance of intrafractional means for each patient. A population standard deviation for each of the five parameters for intra- and interfractional variations were determined. The simulation to treatment setup errors were calculated for all five variables. RESULTS: Lung area variation was 1.50 and 4.19 cm(2) [1 standard deviation (SD)] for intra- and interfractional movement. Intrafractional variation for the other four variables ranged from 0.85 mm for ICM to 2.1 mm (1 SD) for CBD, while interfractional variations ranged from 3.2 to 6.25 mm for CBD and ICM, respectively. The simulation-to-treatment setup variation was greater than the interfractional variation for three of the five variables and was similar for the other two. CONCLUSIONS: On-line verification of intrafractional variation shows a moderate deviation from the treatment setup position for all five parameters studied, while interfractional variation showed even greater deviations for these five parameters. To cover the breast target in 95% of cases, margins of 7.70, 7.70, and 10.30 mm corresponding to the CLD, CFD, and ICM distances, respectively, are required.

Lhermitte's sign: incidence and treatment variables influencing risk after irradiation of the cervical spinal cord.

PURPOSE: Lhermitte's sign is a relatively infrequent sequela of irradiation of the cervical spinal cord. In this study, we sought to determine whether various treatment parameters influenced the likelihood of developing Lhermitte's sign. METHODS AND MATERIALS: Between October 1964 and December 1987, 2901 patients with malignancies of the upper respiratory tract were treated at the University of Florida. The dose of radiation to the cervical spinal cord was calculated for those patients who had a minimum 1-year follow-up. A total of 1112 patients who received a minimum of 3000 cGy to at least 2 cm of cervical spinal cord were included in this analysis. RESULTS: Forty patients (3.6%) developed Lhermitte's sign. The mean time to development of Lhermitte's sign after irradiation was 3 months, and the mean duration of symptoms was 6 months. No patient with Lhermitte's sign developed transverse myelitis. Several variables were examined in a univariate analysis, including total dose to the cervical spinal cord, length of cervical spinal cord irradiated, dose per fraction, continuous-course compared with split-course radiotherapy, and once-daily compared with twice-daily irradiation. Only two variables proved to be significant. Six (8%) of 75 patients who received > or = 5000 cGy to the cervical spinal cord developed Lhermitte's sign compared with 34 (3.3%) of 1037 patients who received < 5000 cGy (p = .04). For patients treated with once-daily fractionation, 28 (3.4%) of 821 patients who received < 200 cGy per fraction developed Lhermitte's sign compared with 6 (10%) of 58 patients who received > or = 200 cGy (p = .02). CONCLUSION: An increased risk of developing Lhermitte's sign was demonstrated for patients who received either > or = 200 cGy per fraction (one fraction per day) or > or = 5000 cGy total dose to the cervical spinal cord.

The influence of lymphangiography on the development of hypothyroidism in patients irradiated for Hodgkin's disease.

PURPOSE: There is no consensus in the literature regarding the role of lymphangiography in promoting hypothyroidism in individuals with Hodgkin's disease irradiated with a mantle field. We sought to analyze the onset and rate of developing clinical or chemical hypothyroidism as well as possible factors related to its development in patients who received irradiation to the thyroid gland during treatment of Hodgkin's disease. METHODS AND MATERIALS: One hundred and forty-two patients with Hodgkin's disease were treated at the Fox Chase Cancer Center between June 1967 and October 1993. All patients were treated with curative intent with radiation therapy using a mantle field. After exclusion of patients without available thyroid function tests, < 200 days of follow-up, or no radiation to the thyroid, 104 patients were eligible for analysis. Follow-up ranged from 7-170 months (median: 43 months). Sixty-seven patients had a lymphangiogram. Seventy-three patients were treated with radiation alone and 31 with radiation plus chemotherapy. RESULTS: The actuarial 2-, and 5-year rates of biochemical hypothyroidism for all 104 patients were 18 and 37%, respectively. Forty patients developed hypothyroidism: 9 (23%) at < or = 1 year, 18 (45%) at < or = 2 years, and 33 (83%) at < or = 5 years. The actuarial 2-, and 5-year rates of biochemical hypothyroidism for patients who underwent a lymphangiogram were 23 and 42%, respectively, compared to 9 and 28%, respectively, for patients who received mantle irradiation without a lymphangiogram (p = 0.05). The effects of lymphangiogram, total thyroid dose, stage, chemotherapy, dose per fraction, energy, and age were evaluated for all patients by Cox proportional hazards regression analysis. The use of a lymphangiogram (p = 0.05) was the only variable that significantly influenced hypothyroidism. CONCLUSIONS: This paper demonstrates in a multivariate analysis accounting for other potentially important variables the significant effect of lymphangiography and subsequent radiation therapy on the development of hypothyroidism. This information must be balanced with the fact that lymphangiograms remain a useful aid in assessing lymph node involvement, staging patients, and planning treatment fields.

The value of setup portal films as an estimate of a patient's position throughout fractionated tangential breast irradiation: an on-line study.

PURPOSE: To determine if portal setup films are an accurate representation of a patient's position throughout the course of fractionated tangential breast irradiation. METHODS AND MATERIALS: Thirteen patients undergoing external beam irradiation for T1-T2 infiltrating ductal carcinoma of the breast following excisional biopsy and axillary dissection were imaged using an on-line portal imaging device attached to a 6 MV linear accelerator. Medial and lateral tangential fields were imaged and a total of 139 fractions, 225 portal fields, and 4450 images were obtained. Interfractional and intrafractional variations for anatomical parameters including the central lung distance (CLD), central flash distance (CFD), and inferior central margin (ICM) were calculated from these images. A pooled estimate of the random error associated with a given treatment was determined by adding the interfractional and intrafractional standard deviations in quadrature. A 95% confidence level assigned a value of two standard deviations of the random error estimate. Central lung distance, CFD, and ICM distances were then measured for all portal setup films. Significant differences were defined as occurring when the simulation-setup difference was greater than the 95% confidence value. RESULTS: Differences between setup portal and simulation films were less than their 95% confidence values in 70 instances indicating that in 90% of the time these differences are a result of random differences in daily treatment positioning. CONCLUSIONS: In 90% of cases tested, initial portal setup films are an accurate representation of a patients daily treatment setup.

Management of retroperitoneal sarcomas: does dose escalation impact on locoregional control?

PURPOSE: Only 50% of patients with retroperitoneal sarcomas undergo complete resection and of these, 47% develop local tumor recurrence. To determine whether irradiation with dose escalation improves locoregional control, we reviewed the experience with adjuvant radiotherapy in the treatment of retroperitoneal sarcomas at the Fox Chase Cancer Center and the Hospital of the University of Pennsylvania. METHODS AND MATERIALS: Twenty-one patients with retroperitoneal sarcomas were treated with curative intent with surgical resection and radiation therapy at Fox Chase Cancer Center or the Hospital of the University of Pennsylvania between May 1965 and July 1992. Follow-up ranged from 14-340 months. Nineteen patients were treated postoperatively and 2 preoperatively. Radiation doses were between 36.0 Gy and 90.0 Gy (median 54.0 Gy). RESULTS: The 2-year rates of local control and survival were 72% and 69%, respectively. Tumor size, stage, grade, and histology did not influence local control. Two of eight patients (25%) who received a total dose of > 55.2 Gy experienced local failure compared to 5 of 13 (38%) who received < or = 55.2 Gy. One patient experienced a small bowel obstruction that required surgical intervention. There were no other severe complications. CONCLUSION: Postoperative treatment with radiotherapy using a dose > 55.0 Gy is recommended for patients with retroperitoneal sarcomas following surgical resection due to the significant likelihood of local recurrence. Innovative adjuvant radiation techniques to escalate doses to greater than 55.0 Gy including intraoperative radiation therapy, brachytherapy, or use of small bowel exclusion devices to reduce small bowel toxicity should be considered for retroperitoneal sarcomas.

Carcinoma in situ of the glottic larynx: the role of radiotherapy.

PURPOSE: To examine the University of Florida experience with radiotherapy of carcinoma in situ of the true vocal cord and compare our results with those reported in other series using various treatment modalities. METHODS AND MATERIALS: Nineteen patients with carcinoma in situ of the true vocal cord were treated with curative intent with radiation therapy at the University of Florida between October 1964 and September 1990. All patients had a minimum 2-year follow-up. Before the radiotherapy, four patients had undergone a biopsy only, 11 patients had undergone one stripping procedure, and four patients had undergone 2 to 5 strippings. Radiation doses were between 5625 cGy and 6300 cGY (median, 5625 cGy). RESULTS: The 5-year rates of local control, ultimate local control, and local control with voice preservation were 93%, 100%, and 93%, respectively. A literature review revealed that local control rates after primary treatment with radiotherapy, laser resection, and vocal cord stripping were 84%, 68%, and 66%, respectively. CONCLUSION: Primary treatment with radiotherapy should be strongly considered for patients with carcinoma in situ of the true-vocal cord who have a recurrence after vocal cord stripping or who cannot have close follow-up after treatment.

Pharyngeal wall carcinoma treated with radiotherapy: impact of treatment technique and fractionation.

PURPOSE: To determine whether a modification in treatment technique and the routine use of twice-daily fractionation have influenced the likelihood of local control in carcinomas of the hypopharyngeal and/or oropharyngeal wall. METHODS AND MATERIALS: Between October 1964 and July 1990, 99 patients with invasive, previously untreated T1-T4 squamous cell carcinoma of the pharyngeal wall were treated with continuous-course, external-beam radio-therapy with curative intent at the University of Florida. All patients had a minimum 2-year follow-up. RESULTS: The 2-year local control rates for patients treated with once-daily vs. twice-daily fractionation were T1, 100% each; T2, 67% vs. 92%; T3, 43% vs. 80%; and T4, 17% vs. 50%. The 2-year local control rates for patients treated with our former technique (posterior border placed at middle of the vertebral body when the portals were reduced off the spinal cord) vs. our current, modified technique (posterior border placed at posterior edge of the vertebral body) were T1, 100% each; T2, 57% vs. 100%; T3, 46% vs. 73%; and T4, 29% vs. 75%. The parameters of T stage, fractionation schedule, primary site, (oropharynx vs. hypopharynx) treatment technique, and lateral vs. posterior pharyngeal wall location were evaluated in a multivariate analysis for the end point of local control. T stage (p = .003), fractionation schedule (p = .001), and primary site (p = .028) were of independent prognostic significance. CONCLUSION: Twice-daily fractionation was the most important treatment-related variable in this patient population.

Dosimetric comparison of treatment planning systems in irradiation of breast with tangential fields.

PURPOSE: The objectives of this study are: (1) to investigate the dosimetric differences of the different treatment planning systems (TPS) in breast irradiation with tangential fields, and (2) to study the effect of beam characteristics on dose distributions in tangential breast irradiation with 6 MV linear accelerators from different manufacturers. METHODS AND MATERIALS: Nine commercial and two university-based TPS are evaluated in this study. The computed tomographic scan of three representative patients, labeled as "small", "medium" and "large" based on their respective chest wall separations in the central axis plane (CAX) were used. For each patient, the tangential fields were set up in each TPS. The CAX distribution was optimized separately with lung correction, for each TPS based on the same set of optimization conditions. The isodose distributions in two other off-axis planes, one 6 cm cephalic and the other 6 cm caudal to the CAX plane were also computed. To investigate the effect of beam characteristics on dose distributions, a three-dimensional TPS was used to calculate the isodose distributions for three different linear accelerators, the Varian Clinac 6/100, the Siemens MD2 and the Philips SL/7 for the three patients. In addition, dose distributions obtained with 6 MV X-rays from two different accelerators, the Varian Clinac 6/100 and the Varian 2100C, were compared. RESULTS: For all TPS, the dose distributions in all three planes agreed qualitatively to within +/- 5% for the "small" and the "medium" patients. For the "large" patient, all TPS agreed to within +/- 4% on the CAX plane. The isodose distributions in the caudal plane differed by +/- 5% among all TPS. In the cephalic plane in which the patient separation is much larger than that in the CAX plane, six TPS correctly calculated the dose distribution showing a cold spot in the center of the breast contour. The other five TPS showed that the center of the breast received adequate dose. Isodose distributions for 6 MV X-rays from three different accelerators differed by about +/- 3% for the "small" patient and more than +/- 5% for the "large" patient. For two different 6 MV machines of the same manufacturer, the isodose distribution agreed to within +/- 2% for all three planes for the "large" patient. CONCLUSION: The differences observed among the various TPS in this study were within +/- 5% for both the "small" and the "medium" patients while doses at the hot spot exhibit a larger variation. The large discrepancy observed in the off-axis plane for the "large" patient is largely due to the inability of most TPS to incorporate the collimator angles in the dose calculation. Only six systems involved agreed to within +/- 5% for all three patients in all calculation planes. The difference in dose distributions obtained with three accelerators from different manufacturers is probably due to the difference in beam profiles. On the other hand, the 6 MV X-rays from two different models of linear accelerators from the same manufacturer have similar beam characteristics and the dose distributions are within +/- 2% of each other throughout the breast volume. In general, multi-institutional breast treatment data can be compared within a +/- 5% accuracy.

Dose estimation to critical organs from vertex field treatment of brain tumors.

PURPOSE: Radiation management of intracranial tumors may require a noncoplanar vertex field that often irradiates the entire length of the body. In view of radiation related risks to the normal tissues dose estimation to the extracranial organs such as the thyroid gland, spinal cord, heart, and genitalia is performed for a vertex field. METHODS AND MATERIALS: A vertex field used clinically was reproduced on an anthropomorphic Rando phantom to measure radiation dose to various organs in the primary beam. Three photon beams (4, 6, and 10 MV), and two high energy electron beams (16 and 20 MeV) were used. Dosimetry was performed with an ion chamber sandwiched between phantom slices at the appropriate positions. All doses were normalized to the target dose at a depth of 5 cm. The effect of the head position was studied by rotating the gantry angle up to +/-20 degrees to mimic the extension and flexion of the head. Theoretical calculation was performed using an exponential best fit to the depth dose table to estimate the dose to various points and compare with the measured dose. RESULTS: The measured normalized dose to the cervical cord, thyroid, heart, and female and male gonads are 60, 36, 16, 2.5, and 1.6%, respectively, for a 6 MV photon beam. The dose from 4 MV and 10 MV are slightly lower and higher, respectively. Doses from electron beams are about a factor of 4-10 lower than those of the photon beams. The measured gonadal dose from the primary beam is <5% of the target dose for all energies used in the study. The actual value, however, is dependent on the body structure, length, and the posture of the patient. A +5 degree head flexion had little effect on the dose to the various parts of the body. The head rotations greater than +/-10 degrees produced relatively lower doses by a factor of 10(-2) to the organs at distances greater than 40 cm from the prescription point. The radiation doses to the different critical organs estimated from the fitted curves are lower than the measured doses up to 35%. CONCLUSIONS: When a vertex field is used for the treatment of the brain tumors, the entire axial length of the body is irradiated which adds to the integral dose. Unlike the scattered and leakage radiation, the primary dose to extracranial critical organs is greater for higher energies. For a 10 MV beam the ovary and testis at a distance of 80 cm and 90 cm may receive a dose of 4.2 and 3%, respectively, of the target dose. The gonadal dose could be quite significant if the entire treatment is delivered using a vertex field. For pediatric and smaller patients, dose to the critical organs at known distances could be estimated from the empirical equation obtained from the measured data. While the risk-benefit ratio is often evaluated and acceptable for treating malignant tumors, the long-term complications need thorough assessment in younger and curable patients. In view of radiation carcinogenesis and genetic burden, dose reduction to critical organs should be considered using a 3D planning system to arrange beams in other nonaxial planes and by considering electron beams for the vertex field.

Results of conservative surgery and radiation for mammographically detected ductal carcinoma in situ (DCIS).

PURPOSE: The role of conservative surgery and radiation for mammographically detected ductal carcinoma in situ (DCIS) is controversial. In particular, there is little data for outcome with radiation in a group of patients comparable to those treated with local excision and surveillance (mammographic calcifications < or = 2.5 cm, negative resection margins, negative postbiopsy mammogram). This study reports outcome of conservative surgery and radiation for mammographically detected DCIS with an emphasis on results in patients considered candidates for excision alone. METHODS AND MATERIALS: From 1983 to 1992, 110 women with mammographically detected DCIS (77% calcifications +/- mass) and no prior history of breast cancer underwent needle localization and biopsy with (55%) or without a reexcision and radiation. Final margins of resection were negative in 62%, positive 7%, close 11%, and unknown 20%. The median patient age was 56 years. The most common histologic subtype was comedo (54%), followed by cribriform (22%). The median pathologic tumor size was 8 mm (range 2 mm to 5 cm). Forty-seven percent of patients with calcifications only had a negative postbiopsy mammogram prior to radiation. Radiation consisted of treatment to the entire breast (median 50.00 Gy) and a boost to the primary site (97%) for a median total dose of 60.40 Gy. RESULTS: With a median follow-up of 5.3 years, three patients developed a recurrence in the treated breast. The median interval to recurrence was 8.8 years and all were invasive cancers. Two (67%) occurred outside the initial quadrant. The 5- and 10-year actuarial rates of recurrence were 1 and 15%. Cause-specific survival was 100% at 5 and 10 years. Contralateral breast cancer developed in two patients. There were too few failures for statistical significance to be achieved with any of the following factors: patient age, family history, race, mammographic findings, location primary, pathologic size, histologic subtype, reexcision, or final margin status. However, young age, positive or close margins, and the presence of a mass without calcifications had a trend for an increased risk of recurrence. There were no recurrences in the subset of 16 patients who would be candidates for surveillance by Lagios' criteria. CONCLUSION: For selected patients, conservative surgery and radiation for mammographically detected DCIS results in a low risk of recurrence in the treated breast and 100% 5- and 10-year cause-specific survival. Improved mammographic and pathologic evaluation results in better patient selection and reduces the risk of the subsequent appearance of DCIS in the biopsy site. The identification of risk factors for an ipsilateral invasive breast recurrence is evolving.

The impact of tamoxifen on breast recurrence, cosmesis, complications, and survival in estrogen receptor-positive early-stage breast cancer.

PURPOSE: To evaluate the impact of tamoxifen on breast recurrence, cosmesis, complications, overall and cause-specific survival in women with Stage I-II breast cancer and estrogen receptor positive tumors undergoing conservative surgery and radiation. METHODS AND MATERIALS: From 1982 to 1991, 491 women with estrogen receptor positive Stage I-II breast cancer underwent excisional biopsy, axillary dissection, and radiation. The median age of patient population was 60 years with 21% < 50 years of age. The median follow-up was 5.3 years (range 0.1 to 12.8). Sixty-nine percent had T1 tumors and 83% had histologically negative axillary nodes. Re-excision was performed in 49% and the final margin of resection was negative in 64%. One hundred fifty-four patients received tamoxifen and 337 patients received no adjuvant therapy. None of the patients received adjuvant chemotherapy. RESULTS: There were no significant differences between the two groups for age, race, clinical tumor size, histology, the use of re-excision, or median total dose to the primary. Patients who received tamoxifen were more often axillary node positive (44% tamoxifen vs. 5% no tamoxifen), and, therefore, a greater percentage received treatment to the breast and regional nodes. The tamoxifen patients less often had unknown margins of resection (9% tamoxifen vs. 22% no tamoxifen). The 5-year actuarial breast recurrence rate was 4% for the tamoxifen patients compared to 7% for patients not receiving tamoxifen (p = 0.21). Tamoxifen resulted in a modest decrease in the 5-year actuarial risk of a breast recurrence in axillary node-negative patients, in those with unknown or close margins of resection, and in those who underwent a single excision. Axillary node-positive patients had a clinically significant decrease in the 5-year actuarial breast recurrence rate (21 vs. 4%; p = 0.08). The 5-year actuarial rate of distant metastasis was not significantly decreased by the addition of adjuvant tamoxifen in all patients or pathologic node-negative patients. Pathologically node-positive patients had a significant decrease in distant metastasis (35 vs. 11%; p = 0.02). There were no significant differences in cause-specific survival for patients receiving tamoxifen when compared to observation (95% no tamoxifen vs. 89% tamoxifen; p = 0.24). Similar findings were noted for pathologically node-negative patients. However, axillary node-positive patients receiving tamoxifen had an improvement in 5-year actuarial cause-specific survival (90% tamoxifen vs. 70% no tamoxifen; p = 0.10). Cosmesis (physician assessment) was good to excellent in 85% of the tamoxifen patients compared to 88% of the patients who did not receive tamoxifen. CONCLUSION: The addition of tamoxifen to conservative surgery and radiation in women with Stage I-II breast cancer and estrogen receptor positive tumors resulted in a modest but not statistically significant decrease in the 5-year actuarial risk of a breast recurrence. Tamoxifen significantly decreased the 5-year actuarial risk of distant metastasis in axillary node-positive patients and there was a trend towards improvement in cause-specific survival that was not statistically significant. Tamoxifen did not decrease the 5-year actuarial rate of distant metastasis in axillary node negative, patients and in this group, there was no improvement in cause-specific survival. Tamoxifen did not have an adverse effect on cosmesis or complications.

Do overall treatment time, field size, and treatment energy influence local control of T1-T2 squamous cell carcinomas of the glottic larynx?

PURPOSE: To evaluate treatment and patient related prognostic factors that may influence local control in the treatment of T1-T2 squamous cell carcinoma of the glottic larynx. METHODS AND MATERIALS: One hundred nine patients with invasive, previously untreated T1-T2 squamous cell carcinoma of the glottic larynx were treated with curative intent with radiotherapy at the Fox Chase Cancer Center between June 1980 and November 1991. Follow-up ranged from 26-165 months (mean 83 months). RESULTS: The 2-year local control rates for patients with T1 and T2 lesions were 89% and 80%, respectively. The 2-year local control rate for patients whose overall treatment time was < 50 days was 92% vs. 82% for patients whose overall treatment time was > 50 days (p = 0.07). The 2-year local control rate for patients treated with an irradiated area < 36 cm(2) was 90% compared to 86% in patients who were treated to an area > or = 36 cm(2). The 2-year local control rate for patients treated with 60Co was 83% vs. 92% for patients treated with 6 MV x-ray. Cox proportional hazards regression analysis was performed using the following variables: treatment energy, irradiated area, gender, tobacco pack years, tumor differentiation, overall treatment time, total dose, dose per fraction, and T stage. Overall treatment time (p = 0.05) was the only variable that significantly influenced local control. CONCLUSION: Extending the overall treatment time was found to adversely influence local control. Neither the irradiated area nor treatment energy was found to influence local control in early stage vocal cord carcinoma.

Does the placement of surgical clips within the excision cavity influence local control for patients treated with breast-conserving surgery and irradiation.

PURPOSE: A number of authors have demonstrated the importance of using surgical clips to define the tumor bed in the treatment planning of early-stage breast cancer. The clips have been useful in delineating the borders of the tangential fields, especially for very medial and very lateral lesions as the boost volume. If surgical clips better define the tumor bed, then a reduction in true or marginal recurrences should be appreciated. We sought to compare the incidence of breast recurrence in women with and without surgical clips, controlling for other recognized prognostic factors. METHODS AND MATERIALS: Between 1980 and 1992, 1364 women with clinical Stage I or II invasive breast cancer underwent excisional biopsy, axillary dissection, and definitive irradiation. Median follow-up was 60 months. Median age was 55 years. Seventy-one percent of patients were path NO, 22% had one to three nodes, and 7% had > than four nodes. Sixty-one percent were ER positive and 44% PR positive. Margin status was negative in 62%, positive in 10%, close in 9%, and unknown in 19%. Fifty-seven percent of women underwent a reexcision. Adjuvant chemotherapy + tamoxifen was administered in 29%, and tamoxifen alone in 17%. Surgical clips were placed in the excision cavity in 556 patients, while the other 808 did not have clips placed. All patients had a boost of the tumor bed. Patients had their boost planned with CT scanning or stereo shift radiographs. No significant differences between the two groups were noted for median age, T stage, nodal status, race, ER/PR receptor status, region irradiated, or tumor location. Patients without clips had negative margins less often, a higher rate of unknown or positive margins and more often received no adjuvant therapy compared to patients with surgical clips. RESULTS: Twenty-five and 27 patients with and without surgical clips, respectively, developed a true or marginal recurrence in the treated breast. The actuarial probability of a breast recurrence was 2% at 5 years and 5% at 10 years for patients without clips compared to 5 and 11%, respectively, for patients with clips (p=0.01). Comparing the breast recurrence rates for patients with and without clips there was no significant difference for the following factors: chemotherapy, tamoxifen, negative, positive or close margins, reexcision, N1, and central or inner primary. Increased rates of breast recurrence were noted for patients with clips for the following variables: no adjuvant treatment (p < 0.001), unknown margins (p < 0.001), a single excision (p = 0.003), path NO (p = 0.001), and outer location (p= 0.02). A forward stepwise multivariate analysis for all 1364 patients was performed using the aforementioned variables as well as the presence or absence of surgical clips and the primary surgeon. The surgeon (p = 0.03) and no adjuvant treatment (p = 0.01) significantly influenced breast recurrence. For patients with surgical clips the 10 year isolated breast recurrence rate was 21% for a single surgeon vs. 6% in the remainder of the group (p = 0.01). For patients with clips, this surgeon had unknown margins in 48% of cases compared to 10% overall (p = 0.001). Excluding this surgeon from analysis the isolated breast recurrence for patients with clips was 6 vs. 5% for patients without clips (p = 0.18). CONCLUSIONS: Overall, there was a significant difference in the 10-year breast recurrence rate favoring women without clips despite more adverse prognostic factors. There was no difference in the breast recurrence rate for patients with or without surgical clips if careful attention to margin status was addressed. Failure to ink the surgical specimen resulting in unknown margins cannot be compensated for with the placement of .

Stage III ovarian carcinoma: an analysis of treatment results and complications following hyperfractionated abdominopelvic irradiation for salvage.

PURPOSE: Patients with persistent disease found at laparotomy following platinum-based chemotherapy for Stage III ovarian carcinoma have a remote chance of cure with second-line chemotherapy or conventional radiotherapy. To decrease relapse rates and improve tolerance, we have used twice-daily radiotherapy in 28 such patients. METHODS AND MATERIALS: Twenty-eight patients with Stage III epithelial ovarian carcinoma were treated with curative intent at the University of Florida with hyperfractionated, continuous-course radiotherapy for persistent disease at laparotomy after administration of platinum-based chemotherapy. All patients received .8 Gy per fraction, twice daily, to a mean total dose of 30.2 Gy to the whole abdomen and pelvis; 20 patients had additional radiotherapy to the pelvis (mean, 14.54 Gy). All patients had undergone two to four (mean, 2.6) laparotomies for ovarian carcinoma and had received 6-28 (mean, 12) cycles of chemotherapy before irradiation. RESULTS: With a 2-year minimum follow-up, survival rates at 1, 2, and 5 years were as follows: absolute survival, 79%, 50%, 21%; relapse-free survival, 52%, 36%, 19%. For the 11 patients with no evidence of gross residual disease after the second-look laparotomy, the absolute survival rates were 100%, 73%, and 27%. This was superior to the rates of 65%, 34%, and 18% for the 17 patients who had gross residual disease. Only two patients required treatment breaks. Four patients required surgical intervention for small-bowel obstruction, which in two cases revealed recurrent disease. Two patients died of treatment-related complications. Twenty-two of 23 failures occurred in the abdomen and/or pelvis. CONCLUSION: Although most patients eventually relapse, a small percentage have had a prolonged disease-free interval. Since treatment was relatively well tolerated, escalation of the dose of hyperfractionated abdominopelvic irradiation is being investigated.

Oropharyngeal carcinoma treated with radiotherapy: a 30-year experience.

PURPOSE: This study was done to determine the outcome in patients with oropharyngeal carcinoma treated at the University of Florida with radiotherapy alone to the primary site, for comparison with reported results of other types of treatment. METHODS AND MATERIALS: Of a consecutive cohort of 785 patients with biopsy-proven, previously untreated, invasive squamous cell carcinoma of the oropharynx, this report is based on the 490 patients who had continuous-course irradiation with curative intent at the University of Florida between October 1964 and January 1991. All patients had a minimum 2-year follow-up. Forty-eight percent had Stage T3 or T4 disease, and 64% had clinically apparent neck node metastases. The median radiation dose was 68 Gy for once-a-day treatment and 76.8 Gy for twice-a-day treatment. Patients with advanced neck node disease had planned neck dissection(s) after radiotherapy. RESULTS: The overall local control rate after radiotherapy alone was 73%. The ultimate local control rate (including surgical salvage) was 78%. At 5 years, the probability of control of neck disease was 85%; control above the clavicles, 67%; absolute survival, 44%; cause-specific survival, 77%; distant metastasis (as the first or only site of failure), 11%. Thirteen patients (2.6%) experienced severe treatment complications. CONCLUSION: Radiotherapy results in tumor control and survival rates comparable with rates achieved with combined irradiation and surgery, with less morbidity.

Management of extremity soft tissue sarcomas with limb-sparing surgery and postoperative irradiation: do total dose, overall treatment time, and the surgery-radiotherapy interval impact on local control?

PURPOSE: To evaluate potential prognostic factors in the treatment of extremity soft tissue sarcomas that may influence local control, distant metastases, and overall survival. METHODS AND MATERIALS: Sixty-seven patients with extremity soft tissue sarcomas were treated with curative intent by limb-sparing surgery and postoperative radiation therapy at the Fox Chase Cancer Center or the Hospital of the University of Pennsylvania, between October 1970 and March 1991. Follow-up ranged from 4-218 months. The median external beam dose was 60.4 Gy. In 13 patients, interstitial brachytherapy was used as a component of treatment. RESULTS: The 5-year local control rate for all patients was 87%. The 5-year local control rate for patients who received < or = 62.5 Gy was 78% compared to 95% for patients who received > 62.5 Gy had larger tumors (p = 0.008) and a higher percentage of Grade 3 tumors and positive margins than patients who received < or = 62.5 Gy. The 5-year local control rate for patients with negative or close margins was 100% vs. 56% in patients with positive margins (p = 0.002). Cox proportional hazards regression analysis was performed using the following variables as covariates: tumor dose, overall treatment time, interval from surgery to initiation of radiation therapy, margin status, grade, and tumor size. Total dose (p = 0.04) and margin status (p = 0.02) were found to significantly influence local control. Only tumor size significantly influenced distant metastasis (p = 0.01) or survival (p = 0.03). CONCLUSION: Postoperative radiation therapy doses > 62.5 Gy were noted to significantly improve local control in patients with extremity soft tissue sarcomas. This is the first analysis in the literature to demonstrate the independent influence of total dose on local control of extremity soft tissue sarcomas treated with adjuvant postoperative irradiation.

A close or positive margin after mastectomy is not an indication for chest wall irradiation except in women aged fifty or younger.

INTRODUCTION: Indications for postmastectomy radiation include primary tumor size > or = 5 cm and/or > or = 4 positive axillary nodes. In clinical practice, patients with a close or positive margin after mastectomy are also often treated with postmastectomy radiation. However, there is little data regarding the risk of a chest wall recurrence in patients with close or positive margins who otherwise would be considered low risk (tumor size <5 cm and/or 0-3 positive nodes). To address this issue, we assessed the risk of a chest wall recurrence in women with Stage I-II breast cancer who underwent mastectomy and were found to have primary tumor size <5 cm and 0-3 positive nodes with a close or positive deep margin. METHODS AND MATERIALS: The pathologic reports from 789 patients treated by mastectomy between 1985 and 1994 at our institution were retrospectively reviewed. Of these, 136 (17%) had tumor within 1 cm of the deep resection margin. The study population consists of 34 of these patients with close or positive margins whose primary tumor size was <5 cm with 0-3 positive axillary nodes and who received no postoperative radiation. The median age was 43 years (range 29-76). Of these, 44% had T1 tumors and 56% T2 tumors. Pathologic axillary nodal status was negative in 65% and positive in 35%. The median number of positive nodes was 1. The deep margin was positive in 2 patients, < or = 2 mm in 17 patients, 2.1-4 mm in 7 patients and 4.1-6 mm in 8 patients. Of the 34 patients, 67% received adjuvant chemotherapy +/- tamoxifen and 21% received tamoxifen alone. The median follow-up was 59 months (range 7-143). RESULTS: There were 5 chest wall recurrences at a median interval of 26 months (range 7-127). One was an isolated first failure, one occurred concurrent with an axillary recurrence, and three were associated with distant metastases. The 5- and 8-year cumulative incidences of a chest wall recurrence were 9% and 18%. Patient age correlated with the cumulative incidence of chest wall recurrence at 8 years; age < or = 50 years had a rate of 28% vs. 0% for age >50 (p = 0.04). There was no correlation with chest wall failure and number of positive nodes, ER status, lymphovascular invasion, location of primary, grade, family history, or type of tumor close to the margin. Of 5 chest wall failures, 4 were in patients who had received adjuvant systemic chemotherapy +/- tamoxifen. Chest wall failures occurred in 1 patient with a positive deep margin, 3 patients with margins within 2 mm, and 1 patient with a margin of 5 mm. The estimated cumulative incidence probability of chest wall recurrence at 8 years by margin proximity was 24% < or = 2 mm vs. 7% 2.1-6 mm (p = 0.36), and by clinical size 24% for T2 tumors vs. 7% for T1 (p = 0.98). CONCLUSIONS: A close or positive margin is uncommon (< or = 5%) after mastectomy in patients with tumor size <5 cm and 0-3 positive axillary nodes but, when present, it appears to be in a younger patient population. The subgroup of patients aged 50 or younger with clinical T1-T2 tumor size and 0-3 positive nodes who have a close (< or = 5 mm) or positive mastectomy margin are at high risk (28% at 8 years) for chest wall recurrence regardless of adjuvant systemic therapy and, therefore, should be considered for postmastectomy radiation.