High risk of breast carcinoma after irradiation of young women with Hodgkin's disease.

BACKGROUND: Treatment-associated second neoplasms have emerged as a major threat to the continued survival of patients cured of Hodgkin's disease. In this study, the authors investigated the risk of breast carcinoma in an irradiated Hodgkin's disease population. METHODS: One hundred and eleven women younger than 60 years presenting between 1964 and 1984 with Stage I and II Hodgkin's disease who received mantle irradiation were retrospectively analyzed and compared with an age specific population. Median follow-up was 18 years (range, 10-30 years), and the median age at initiation of therapy was 24 years. Kaplan-Meier actuarial risks, relative risks (RRs) (the ratio of the observed to the expected cases) with 95% confidence intervals (CIs), and the log rank test for trends were calculated. RESULTS: Fourteen women developed breast carcinoma: 8 of 33 patients younger than 20 years at the time of irradiation, 5 of 48 patients age 20 to 29 years, and 1 of 30 patients age 30 years or older. Actuarial calculation predicted a 34.0% (CI, 14.2-53.8) risk of breast carcinoma at 25 years after therapy for the youngest group, 22.3% (CI, 4.1-40.5) for the group of intermediate age, and 3.5% (CI, 0-10.1) for the oldest group. The RR of breast carcinoma was 56 (CI, 23.3-107) for those 19 years or younger at the time of treatment, 7.0 (CI, 2.3-16.4) for those age 20-29 years, and 0.9 (CI, 0-5.3) for those 30 years and older. Excluding 1 patient who was age 38 years at the time of irradiation, the remaining 13 breast carcinomas were tightly clustered in women irradiated between the ages of 14 through 25, and were detected in years 11 through 25 after treatment, with 7 occurring in years 15 through 18. CONCLUSIONS: Women younger than 30 years, particularly those younger than 20 years, who have received mantle irradiation for Hodgkin's disease require meticulous follow-up for breast carcinoma. The high incidence of breast carcinoma in this patient population should be considered when making treatment decisions in young women with early stage Hodgkin's disease.

A survey of radiation oncologists regarding their radiation physics instruction.

The American Association of Physicists in Medicine, Committee on Training of Radiologists conducted a survey of radiation oncologists requesting information regarding their radiation oncology physics training. General questions were asked of the oncologist regarding their radiation oncology practice such as number of oncologists, number of new patients treated, and the size and type of facility in which the practice is located. The oncologist also responded to questions regarding their educational background. The survey requested the radiation oncologists to answer questions regarding the adequacy and importance of their training in specific areas of radiation physics. The responders indicated that the importance of most physics topics in their clinical practice corresponded to the level of their understanding. The survey indicated that for most radiation oncologists their physics instruction was an important and interesting part of their residency program.

Three-dimensional treatment planning for para-aortic node irradiation in patients with cervical cancer.

Three-dimensional treatment planning has been used by four cooperating centers to prepare and analyze multiple treatment plans on two cervix cancer patients. One patient had biopsy-proven and CT-demonstrable metastasis to the para-aortic nodes, while the other was at high risk for metastatic involvement of para-aortic nodes. Volume dose distributions were analyzed, and an attempt was made to define the role of 3-D treatment planning to the para-aortic region, where moderate to high doses (50-66 Gy) are required to sterilize microscopic and gross metastasis. Plans were prepared using the 3-D capabilities for tailoring fields to the target volumes, but using standard field arrangements (3-D standard), and with full utilization of the 3-D capabilities (3-D unconstrained). In some but not all 3-D unconstrained plans, higher doses were delivered to the large nodal volume and to the volume containing gross nodal disease than in plans analyzed but not prepared with full 3-D capability (3-D standard). The small bowel was the major dose limiting organ. Its tolerance would have been exceeded in all plans which prescribed 66 Gy to the gross nodal mass, although some reduction in small bowel near-maximum dose was achieved in the 3-D unconstrained plans. All plans were able to limit doses to other normal organs to tolerance levels or less, with significant reductions seen in doses to spinal cord, kidneys, and large bowel in the 3-D unconstrained plans, as compared to the 3-D standard plans. A high probability of small bowel injury was detected in one of four 3-D standard plans prescribed to receive 50 Gy to the large para-aortic nodal volume; the small bowel dose was reduced to an acceptable level in the corresponding 3-D unconstrained plan. An optimum beam energy for treating this site was not identified, with plans using 4, 6, 10, 15, 18, and 25 MV photons all being equally acceptable. Attempts to deliver moderate or high doses (50-66 Gy) to this region should be made only after careful analysis of the plan with techniques similar to those employed in this study.

Interinstitutional experience in verification of external photon dose calculations.

Under the auspices of NCI contracts, four institutions have collaborated to assess the accuracy of the pixel-based dose calculation methods they employ for external photon treatment planning. The approach relied on comparing calculations using each group's algorithm with measurements in phantoms of increasing complexity. The first set of measurements consisted of ionization chamber measurements in water phantoms in normally incident square fields, an elongated field, a wedged field, a blocked field, and an obliquely incident beam. The second group of measurements was carried out using thermoluminescent dosimeters in phantoms designed to investigate the effects of surface curvature, high density heterogeneities, and low density heterogeneities. The final study tested the entire treatment planning system, including CT data conversion, in an anthropomorphic phantom. Overall, good agreement between calculation and measurements was found for all algorithms. Regions in which discrepancies were observed are pointed out, areas for algorithm improvement are identified and the clinical import of algorithm accuracy is discussed.

Numerical scoring of treatment plans.

This is a report on numerical scoring techniques developed for the evaluation of treatment plans as part of a four-institution study of the role of 3-D planning in high energy external beam photon therapy. A formal evaluation process was developed in which plans were assessed by a clinician who displayed dose distributions in transverse, sagittal, coronal, and arbitrary oblique planes, viewed dose-volume histograms which summarized dose distributions to target volumes and the normal tissues of interest, and reviewed dose statistics which characterized the volume dose distribution for each plan. In addition, tumor control probabilities were calculated for each biological target volume and normal tissue complication probabilities were calculated for each normal tissue defined in the agreed-upon protocols. To score a plan, the physician assigned a score for each normal tissue to reflect possible complications; for each target volume two separate scores were assigned, one representing the adequacy of tumor coverage, the second the likelihood of a complication. After scoring each target and normal tissue individually, two summary scores were given, one for target coverage, the second reflecting the impact on all normal tissues. Finally, each plan was given an overall rating (which could include a downgrading of the plan if the treatment was judged to be overly complex).

Conjunctival lymphoma: results and treatment with a single anterior electron field. A lens sparing approach.

Lymphoma of the conjunctiva is rare. It presents in older patients as a mass lesion and usually remains localized. Surgery is limited to biopsy, and radiation therapy is the definitive treatment of choice. The entire conjunctiva is treated. Relatively high doses (approximately 30 Gy) are required for local control, which may lead to cataract formation. Twelve patients with conjunctival lymphoma were treated at the Massachusetts General Hospital between 1979 and 1988. Ten of 12 patients presented with a unilateral lesion; 2 of 12 with bilateral lesions. Two of 12 patients were found to have systemic disease at the time of presentation. One patient developed conjunctival lymphoma 5 years after the diagnosis of generalized disease. Using electron beam, all patients were treated with a single anterior circular field to total doses ranging from 24 Gy to 30 Gy delivered in 8 to 16 fractions over 9 to 20 days. In all cases, the lens was shielded by a specially designed plastic contact lens bearing a 12 mm diameter lead shield. The lens dose was determined at varying depths beneath the shield for 6 MeV and 9 MeV electron beams and ranged from a minimum of 5% to an absolute maximum of 18% of the total dose delivered to the tumor. Local control was maintained in all patients with follow-up to 9 1/2 years. One patient relapsed distantly 3 years after treatment. One of 12 patients died of systemic disease 4 years after treatment of the ocular lesion. Two patients developed cataracts 4 and 5 years after treatment; one had bilateral cataract, although only one eye had been treated. Both patients were over 75 years old. In both cases, the cataracts were felt to be senile cataracts which are ophthalmologically and radiographically distinguishable from radiation induced lesions.

A survey of the information gained from planning treatment with a computer.

We designed a questionnaire to be filled out by the physicist at the time of planning treatment with the aid of a computer in order to assess what was learned during the course of the planning session. We analyzed the results to gauge the impact of the 70 treatment planning sessions conducted during the one month period in our department in which questionnaires were completed (about 72% of all external beam plans made in that period). In 65 instances (93%) an initial judgment as to how treatment would be delivered had already been made and in 56 of these cases the patient's treatment had already been simulated by the time the computer calculation was made. Changes in the intended plan were made in eight of the 65 cases (12%). In 38% of the cases, more than one plan was developed and, when this was the case, on average records of 2.6 plans were made. Those performing the plans were asked to judge their value to the overall treatment of the patient, and the results were as follows: essential-19 cases (27%); very helpful-22 cases (31%); and somewhat helpful-29 cases (41%).

Variation in the lung inhomogeneity correction factor with beam energy. Clinical implications.

In order to determine the magnitude of the dosimetry error introduced by failing to correct for increased transmission through lung tissue in treating thoracic malignancies, measurements in a phantom were taken using different field sizes, inhomogeneity thicknesses and photon qualities. The results indicate that the error introduced by neglecting the inhomogeneity correction is greatest at lower photon energies, smaller field sizes and greater thickness of inhomogeneity. Correction factors to account for the lung inhomogeneity were obtained from phantom measurements and were compared with those calculated using the tissue-air ratio and Batho-Young algorithms; correlation coefficients describing the relationship between measured and calculated values exceeded 0.995. The calculated values tended to overestimate the correction factor and differed most from the measured correction factors at lower energies, smaller field sizes, and greater inhomogeneity thicknesses. The importance of these results in clinical radiation therapy is discussed.

Treatment planning for colorectal cancer: radiation and surgical techniques and value of small-bowel films.

For colorectal cancer, the adjuvant radiation dose levels required to achieve a high incidence of local control closely parallel the radiation tolerance of small bowel (4500-5000 rad), and for patients with partially resected or unresected disease, the dose levels exceed tolerance (6000-7000 rad). Therefore, both the surgeon and the radiation oncologist should use techniques that localize tumor volumes and decrease the amount of small intestine within the irradiation field. Surgical options include pelvic reconstruction (reperitonealization, omental flaps, retroversion of uterus, etc.) and clip placement. Radiation options include the use of radiographs to define small bowel location and mobility combined with treatment techniques using multiple fields, bladder distention, shrinking or boost fields, and/or patient position changes (prone, decubitus, etc.). When both specialties interact in optimum fashion, local control can be increased with minimal risks to achieve a suitable therapeutic ratio.

Combined surgery and postoperative radiation therapy for advanced laryngeal and hypopharyngeal carcinomas.

The survival, pattern of failure and complications in 47 patients with Stage III and IV cancers of the glottis, supraglottis and hypopharynx treated with surgery and postoperative radiotherapy using a new treatment technique referred to as "mini-mantle" were analyzed. The absolute survival probability of the entire group was 53 and 31% at 3 and 5 years. The local control probability at 3 and 5 years was 63 and 58%, and was higher for the supraglottic/hypopharyngeal than for glottic carcinomas. Advanced lesions, lymph node metastases and positive resection margins were significantly related to a worse local control. Five patients developed complications requiring surgical correction, but none experienced mortality. Moderate complications were treated conservatively without lasting sequelae. This technique is a reasonably safe and efficient procedure and can be effectively employed for the management of advanced laryngeal and hypopharyngeal carcinomas after definitive surgery.

Intra-oral cone radiation therapy for selected carcinomas of the oral cavity.

A study of 101 patients with early carcinomas of the oral cavity, T1 and T2, treated by external cobalt 60 beam and/or intra-oral cone (IOC) radiation therapy between 1964 through 1980 was made. The two year disease-free survival rate, including surgical salvage, was 88% and the local control rate was 85%. The incidence of radiation complications, i.e. soft tissue ulceration and/or osteoradionecrosis, was 14% and varied with various tumor sites and radiation doses delivered. The present review shows that local control and radiation complications are closely related to radiation doses and varies with different tumor sites of the oral cavity. Radiation therapy dosages expressed in terms of TDF values for these lesions are herein recommended. With proper selections of lesions arising from the oral cavity, combined external beam and IOC radiation therapy has been found extremely efficacious in achieving good local tumor control and high survival rates with excellent cosmetic and functional results and minimum radiation sequelae.

Radiation therapy for primary lymphoma of bone.

The records of 30 patients with primary lymphoma of bone (PLB) who were treated with radiation therapy were reviewed. The probability of NED-survival and overall survival at five-year follow-up was 53 and 63%, respectively. There were three local failures following treatment. The cumulative incidence of local recurrence was 14% at five years. No local failures were observed when tumors received doses higher than 50 Gy, or equivalent to a TDF of 70 or greater. The number of failures was too small to examine for a correlation between histologic subclassification and local control frequency if doses higher than 50 Gy were utilized. Complications of treatment occurred in four patients. Functional results were excellent in all except two patients. These data provide guidelines for determination of a clinically appropriate radiation dose level for PLB.

Primary lymphoma of bone: the relationship of morphologic diversity to clinical behavior.

Since primary lymphoma of bone (PLB) exhibits morphologic diversity and variability in individual survival, we analyzed the relationship between histopathologic features and biological behavior in 33 patients treated at the Massachusetts General Hospital. Three major histologic subgroups were identified, based on a variety of criteria, the most important of which were the predominance of cells with or without nuclear clefts and the degree of pleomorphism. The probability of NED survival at five years was 64% for patients with tumor predominantly composed of cleaved cells, 13% for those with tumors classified in the noncleaved cell tumor group, and 0% (no survivors) for the pleomorphic subgroup. When tumors were subclassified according to the size of the predominant cell (small versus large), this parameter was found to be of no value in preceding NED survival. Factors that could have potentially influenced the results were analyzed. Since this is a retrospective review, the questions addressed in this study should be further studied in a prospective way.

Tissue phantom ratios for a Clinac 4/100.

Tissue phantom ratios (TPR), based on a normalization depth of 5 cm, have been measured in water for field sizes from 5 x 5 cm2 to approximately 40 x 40 cm2 and for depths from 1 to 40 cm for a Varian Clinac 4/100. These TPR's have been compared with those calculated from percent depth doses measured at the same time, and the two sets of data generally agree to better than 1%, with an average ratio of measured to calculated TPR of 0.999 +/- 0.013. Beam profiles have been measured for open and wedged fields, with particular concern for the often observed "horns," or the increase in dose at the corners of the field. The maximum dose at a depth of 1 cm, along the diagonal of the field for this machine, is approximately 5% higher than at the same depth on the central axis, whereas along the principal plane the maximum dose is only about 3% higher.

A wedge filter interlock system for 4 MV linear accelerators.

The wedge filter interlock system on a 4 MV linear accelerator was modified to ensure proper selection and placement of filter. By using a series of microswitches to replace the two-pin connection for each wedge, proper placement of the wedge in the treatment beam was ensured. Both the chain and plug were eliminated by using a 6 pole, 6 position sub-miniature rotary switch to produce the remaining connections.

Malfunction of linear accelerator dose monitoring systems.

Malfunctions of the dose monitoring systems of two linear accelerators were studied. A variation of plus or minus 2.5% over an air density correction factor range from 1.02 to 1.07 was measured, suggesting that the ionization-type monitor chambers were open to the atmosphere. An average variation of minus 2.0% was present between early morning calibrations and those performed later in the day. Any variation caused by changes in control console temperature was within experimental error. This type of malfunction can lead to errors in delivered doses of 5%.