Connecticut Pictorial Learning Test: a pictorial version of the California Verbal Learning Test.

This paper describes the development of a pictorial version of the California Verbal Learning Test. The new instrument, named the Connecticut Pictorial Learning Test (COPLT), was tested in two experiments. The first experiment involved selection and testing of new verbal stimuli to be adapted for pictorial use. Results suggest that these new items are approximately equivalent in difficulty to the original CVLT stimuli. These stimuli can serve as CVLT alternate Form III for use in clinical verbal memory research. Recall means and standard deviations are provided for the new stimulus set with a young adult sample. The second experiment explores the psychometric properties of the new COPLT after stimuli were translated into pictorial form. The psychometric evidence suggests that the pictorial test has good internal consistency and concurrent validity with widely-used clinical memory tests. Furthermore, verbally-mediated information processing serves successful pictorial learning and subsequent recall performance in normal healthy control subjects when verbally-encodable pictorial stimuli are used. The use of semantic organization appears to be even more important for optimal performance using pictorial stimuli than with verbal stimuli. Scoring rules for the COPLT are included in the Appendix.

Subgroups of children with autism by cluster analysis: a longitudinal examination.

OBJECTIVES: A hierarchical cluster analysis was conducted using a sample of 138 school-age children with autism. The objective was to examine (1) the characteristics of resulting subgroups, (2) the relationship of these subgroups to subgroups of the same children determined at preschool age, and (3) preschool variables that best predicted school-age functioning. METHOD: Ninety-five cases were analyzed. RESULTS: Findings support the presence of 2 subgroups marked by different levels of social, language, and nonverbal ability, with the higher group showing essentially normal cognitive and behavioral scores. The relationship of high- and low-functioning subgroup membership to levels of functioning at preschool age was highly significant. CONCLUSIONS: School-age functioning was strongly predicted by preschool cognitive functioning but was not strongly predicted by preschool social abnormality or severity of autistic symptoms. The differential outcome of the 2 groups shows that high IQ is necessary but not sufficient for optimal outcome in the presence of severe language impairment.

Functional magnetic resonance imaging of facial affect recognition in children and adolescents.

OBJECTIVE: To examine further the role of the amygdala in the recognition of facial expression in adolescents. METHOD: Twelve healthy adolescents were studied using functional magnetic resonance imaging technology during a task of facial affect recognition and a visual control task. RESULTS: All subjects demonstrated a significant increase in signal intensity in the amygdala for the facial expression recognition task. CONCLUSIONS: The data are consistent with previous work in healthy adult subjects implicating the amygdala as essential for the recognition of fearful facial expression.

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.

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.

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.

Patterns of dose variability in radiation prescription of breast cancer.

PURPOSE: Comparison of radiation outcome of various treatment protocols is difficult due to the variability of dose prescription. A retrospective analysis of the pattern and intercomparison of dose prescriptions is presented for the treatment of breast cancer. MATERIALS AND METHODS: To represent the clinical practice for breast irradiation with tangential fields, commonly used prescription points were chosen that lie on the perpendicular bisector of the chest wall separation (s) that represents the breast apex height (h). These points are located at 1.5 cm from the posterior beam edge, at the chest wall-lung interface (2-3 cm), at distances of h/3 and h/2, and at the isocenter. One hundred consecutive patients treated with intact breast following excisional biopsy were used in this study. For analysis, treatment planning was carried out without lung correction with a 6 MV beam for all patients, even though some of the patients were treated with high energy beams for dose uniformity. Dose distributions were optimized with wedges and beam weights to provide a symmetrical dose distribution on the central axis plane. The statistical analyses of the different parameters, s, h, maximum dose, and doses at various prescription points were carried out. RESULTS: The maximum dose (hot spot) in breast varied from +5% to +27% above the prescribed dose among the patient population. The hot spot was directly related to s, and appeared to be independent of h and the ratio h/s. Among 55%, 40%, and 5% of the patients, the magnitude of the hot spot was 5-10%, 10-15%, and >15%, respectively. Except for the magnitude of the hot spot, the doses at various prescription points were independent of the breast size. For a prescription point at h/3 or at the lung-chest wall interface, the dose variation within +/- 1% is observed for 90% of the patient population. On the other hand, the average dose variation is about +/- 3% among other protocols with dose prescription point varying up to the h/2 point. With the prescription point at the isocenter, an average and maximum variation of 4-5% and 11% were observed, respectively. The maximum dose inhomogeneity for some patients was significantly higher, i.e. up to +27% even without the lung correction. CONCLUSIONS: A wide variation in prescription dose is observed among the different treatment protocols commonly used in breast treatment. For a total dose of 46-50 Gy delivered at 2 Gy/fraction to the breast, the prescribed dose may vary between 50 and 55 Gy and the hot spot dose per fraction may range between 2.3 and 2.5 Gy depending on the protocol and breast size. Thus dose normalization at hot spot and the isocenter should be discouraged unless the total dose to the breast is modified. A uniform definition of dose prescription for breast treatment is greatly required for intercomparison of clinical data.

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.

Identification of women with T1-T2 breast cancer at low risk of positive axillary nodes.

BACKGROUND AND OBJECTIVES: The diagnostic and therapeutic significance of axillary dissection has been questioned. We sought to define a subgroup of patients with early-stage breast cancer who are at low risk for positive axillary nodes. METHODS: Between 1970 and 1995, 1,598 women with stage I and II breast cancer underwent level I-II axillary dissection with a minimum of 10 nodes removed. The following factors were examined in univariate analysis for predicting positive nodes: race, method of detection, location of the primary tumor, age, menopausal status, obesity, ER status, PR status, pathologic tumor size, lymphatic vascular invasion, tumor grade, and histology. RESULTS: Four hundred and forty-five of the 1,598 patients (27.8%) had histologically positive axillary nodes. Significant factors in univariate analysis for positive nodes included: tumor size, lymphatic vascular invasion, grade, method of detection, primary tumor location, and age. The only group of women with a 0% risk of axillary nodes were those in whom the pathologic tumor size was < or = 5 mm and mammographically detected. A 5-10% risk of positive axillary nodes was identified in women with (1) pathologic tumor size 6-10 mm, mammographically detected, and age < or = 40 years, and (2) tubular carcinoma < or = 10 mm. Tumors detected on physical examination with or without mammography and women < or = 40 years had a significantly increased risk of nodes. In multivariate analysis lymphatic vascular invasion (P < 0.001), method of detection (P = 0.026), location (P = 0.01), and pathologic tumor size (P = 0.002) were significant predictors of positive axillary lymphadenopathy. CONCLUSIONS: The decision to forego an axillary dissection should be considered in (1) tumors mammographically detected and < or = 5 mm (2) mammographically detected, pathologic size 6-10 mm, age > 40 and (3) tubular carcinoma < or = 10 mm. All other groups had a > 10% risk of nodes and may benefit from axillary dissection.

Neck failure in T2N0 squamous cell carcinoma of the true vocal cords: the Fox Chase experience and review of the literature.

There is a need for additional data in the literature regarding elective nodal irradiation in the treatment of T2N0 squamous cell carcinoma of the glottic larynx. We examined the experience at the Fox Chase Cancer Center and performed a literature review in order to define a treatment policy. Sixteen patients with T2 squamous cell carcinoma of the glottic larynx were treated with radiation therapy. Ten patients were irradiated to the larynx alone and six to the larynx and regional nodes. None of the patients in our series experienced a nodal recurrence regardless of whether the neck was electively irradiated. A literature review of 413 patients revealed that 2.6% of patients who did not have their nodes electively irradiated and had their primary tumor controlled experienced a nodal failure compared to 3.7% if the primary and regional nodes were irradiated (P = 0.88). Similarly, there was no significant difference in the rate of nodal failure for patients who experienced a recurrence at the primary site regardless of whether they received elective nodal irradiation (P = 0.36). We recommend treatment to the larynx alone since our policy is to treat the regional nodes only when the incidence of occult lymphadenopathy in the neck exceeds 15%.

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.

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.

Computed tomography-magnetic resonance image fusion: a clinical evaluation of an innovative approach for improved tumor localization in primary central nervous system lesions.

We describe our initial experience with the AcQSim (Picker International, St. David, PA) computed tomography-magnetic resonance imaging (CT-MRI) fusion software in eight patients with intracranial lesions. MRI data are electronically integrated into the CT-based treatment planning system. Since MRI is superior to CT in identifying intracranial abnormalities, we evaluated the precision and feasibility of this new localization method. Patients initially underwent CT simulation from C2 to the most superior portion of the scalp. T2 and post-contrast T1-weighted MRI of this area was then performed. Patient positioning was duplicated utilizing a head cup and bridge of nose to forehead angle measurements. First, a gross tumor volume (GTV) was identified utilizing the CT (CT/GTV). The CT and MRI scans were subsequently fused utilizing a point pair matching method and a second GTV (CT-MRI/GTV) was contoured with the aid of both studies. The fusion process was uncomplicated and completed in a timely manner. Volumetric analysis revealed the CT-MRI/GTV to be larger than the CT/GTV in all eight cases. The mean CT-MRI/GTV was 28.7 cm3 compared to 16.7 cm3 by CT alone. This translated into a 72% increase in the radiographic tumor volume by CT-MRI. A simulated dose-volume histogram in two patients revealed that marginal portions of the lesion, as identified by CT and MRI, were not included in the high dose treatment volume as contoured with the use of CT alone. Our initial experience with the fusion software demonstrated an improvement in tumor localization with this technique. Based on these patients the use of CT alone for treatment planning purposes in central nervous system (CNS) lesions is inadequate and would result in an unacceptable rate of marginal misses. The importation of MRI data into three-dimensional treatment planning is therefore crucial to accurate tumor localization. The fusion process simplifies and improves precision of this task.

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 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.

Phase I/II study of concomitant irradiation and carboplatin for locally advanced carcinoma of the uterine cervix: an interim report.

The outcome of women treated with either definitive irradiation alone or in combination with cisplatin-based chemotherapy for locally advanced (>IIb) squamous cell carcinoma of the cervix has been disappointing. To improve upon our reported results with irradiation alone, a trial using irradiation plus carboplatin chemotherapy was designed for these patients. Twenty-seven women with unresectable squamous cell carcinoma of the uterine cervix were referred to our institution between July 1991 and September 1994. Seven of these patients were enrolled in a phase I/II protocol combining concurrent irradiation and carboplatin chemotherapy. Megavoltage irradiation was used to deliver 45-50.4 Gy to the pelvis (and paraaortic chain when nodes were involved) through a multiple-field technique followed by the application of Fletcher-Suit-Delclos tandem and ovoids to boost the point A dose to 85 Gy. Chemotherapy consisted of intravenous carboplatin (60 mg/m2) administered in conjunction with irradiation to a total dose of 300 mg/m2. The enrolled patients consisted of six women with stage IIIb disease and one with stage IIa with concomitant paraaortic adenopathy. All seven patients enrolled in the study completed the planned course of treatment and tolerated the treatment without severe acute morbidities. No dose modifications were required for the radiation therapy regimen. For one patient, a dose of carboplatin was withheld to allow recovery from thrombocytopenia. The overall response rate was 100% (four complete response, three partial response). The combination of concurrent irradiation (pelvic or pelvic + paraaortic fields) and carboplatin chemotherapy can be safely administered to patients with locally advanced squamous cell carcinoma of the cervix. The treatment is well tolerated and is associated with a high rate of response. Longer follow-up will be necessary to assess the durability of response. In the meantime, we have elected to escalate the dose of carboplatin (90 mg/m2) in the hope of increasing the rate of complete response without incurring unacceptable toxicity.

Salvage surgery after radiotherapy failure in T1-T2 squamous cell carcinoma of the glottic larynx.

BACKGROUND: This study was undertaken to analyze the clinical course of patients who developed local (primary) recurrence after high-dose irradiation of T1 -T2 squamous cell carcinoma of the glottic larynx. METHODS: Between May 1977 and December 1989, 247 patients with previously untreated T1 and T2 invasive squamous cell carcinoma of the glottic larynx were treated for curative intent with radiotherapy. Local recurrence occurred in 26 of 247 patients (11%). Successful surgical salvage was defined as no evidence of recurrent cancer for at least 2 years after salvage surgery and continuously thereafter. RESULTS: Two patients refused to undergo salvage surgery and one patient had unresectable disease. Of 23 patients who underwent salvage surgery, 19 had a total laryngectomy and 4 had a voice-sparing procedure. One patient who was continuously free of disease, died less than 24 months after salvage surgery; this patient was excluded from all local control and survival analyses, leaving 22 patients available for analysis. Successful salvage was achieved initially in 13 (59%) of the 22 patients. Two patients with local failure after voice-sparing salvage surgery underwent completion laryngectomy; one was salvaged, so that 14 of 22 (64%) were ultimately salvaged. The rate of successful salvage did not correlate with preirradiation T stage, time to failure after irradiation, or time from clinical suspicion of recurrence to histologic proof. In a subgroup of patients (those with positive margins, tumor extension into the soft tissues of the neck, or two or more adverse histologic features), the risk of local-regional recurrence after salvage laryngectomy was 80%. CONCLUSION: There are few data in the literature regarding the clinical outcome of patients whose tumors are not controlled by initial radiotherapy. This series and previous publications from other institutions indicate that most patients who develop primary failure undergo salvage surgery, which is successful in approximately 50-80% of the patients. The rate of surgical complications is acceptable and is related to radiotherapy dose. At our institution, most patients who had recurrence after radiotherapy underwent total laryngectomy. More than 50% of the patients who experienced recurrence after irradiation originally had tumors of such extent that they would have required total laryngectomy if surgery had been recommended instead of radiotherapy for the initial treatment. It is reasonable to consider reirradiation in patients with a very high risk of local-regional recurrence after salvage laryngectomy.

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 .

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.