Michael A. Stracher

LARGE SCALE OPTIMIZATION OF BEAM WEIGHTS UNDER DOSE-VOLUME RESTRICTIONS

The problem of choosing weights for beams in a multifield plan which maximizes tumor dose under conditions that recognize the volume dependence of organ tolerance to radiation is considered, and its solution described. Structures are modelled as collections of discrete points, and the weighting problem described as a combinatorial linear program (LP). The combinatorial LP is solved as a mixed 0/1 integer program with appropriate restrictions on normal tissue dose. The method is illustrated through the assignment of weights to a set of 10 beams incident on a pelvic target. Dose-volume restrictions are placed on surrounding bowel, bladder, and rectum, and a limit placed on tumor dose inhomogeneity. Different tolerance restrictions are examined, so that the sensitivity of the target dose to changes in the normal tissue constraints may be explored. It is shown that the distributions obtained satisfy the posed constraints. The technique permits formal solution of the optimization problem, in a time short enough to meet the needs of treatment planners.

Patterns of Failure Following Local Excision and Local Excision and Postoperative Radiation Therapy for Invasive Rectal Adenocarcinoma

The clinical course of 40 patients undergoing conservative surgical excision and 26 patients undergoing local excision and postoperative radiation therapy of rectal carcinoma was reviewed. Surgical procedures were transanal excision (55 patients), Kraske procedure (ten patients), and fulguration (one patient). The five-year actuarial survival, disease-free survival, and local control of all 66 patients were 70%, 77%, and 63%, respectively. For patients undergoing local excision alone, the prognostic features of lesion size greater than 3 cm, poorly differentiated histology, invasion into muscularis propria or deeper, moderate to marked stromal fibrosis, vascular or lymph vessel invasion, fragmented resection, and positive resection margins were associated with a local failure rate of 20% or greater. Of the 26 patients receiving postoperative radiation therapy, four patients have developed local failure. For subgroups of patients with small rectal carcinomas confined to the mucosa, local excision may be a reasonable alternative to abdominoperineal resection. For tumors with deeper invasion but limited to the bowel wall, local excision plus pelvic irradiation can be offered to preserve anorectal function.

Fibromatoses: From postsurgical surveillance to combined surgery and radiation therapy

The results of management of two groups of patients with musculoaponeurotic (desmoid tumors) and plantar fibromatoses seen at Massachusetts General Hospital (MGH) during the period 1970-1985 are examined: (a) 26 patients who had had surgical resection for their primary fibromatosis but whose surgical margins were positive and who received no further treatment; and (b) 24 patients who were treated for their primary or recurrent fibromatosis by radiation alone or combined with surgery. For the 26 patients who were only observed, despite the positive surgical margins, 9 have recurred; the actuarial continuous local control rate at 5 years was 68% (a median follow-up of 70 months). Five patients had gross disease left after surgery and all of them failed. Seventeen of 21 patients who had grossly complete resection have local control; the four failures have been salvaged. This result supports the rationale for a no treatment but a thorough and close follow-up policy for patients with positive margins after grossly complete resection of a primary desmoid or fascial fibromatosis. There is no risk of metastasis in these patients and hence the effort toward a conservative policy which defers radiation merits interest and further study. Of the second group, 23 patients were treated for gross disease and one patient for microscopic disease after surgical resection. All of the 10 patients who were treated for primary desmoid tumor have local control. Among the 14 recurrent desmoid tumors there have been five local failures, after treatment by radiation alone or radiation + surgery. Three patients treated by radiation alone are currently scored as incompletely regressed tumors. Accordingly 16 of the 24 patients are scored as local controls without evidence of disease and 19 of the 24 are scored as local control (complete response or partial but stable response).

The effect of the respiratory cycle on mediastinal and lung dimensions in Hodgkin's disease: implications for radiotherapy gated to respiration

Changes in mediastinal and lung dimensions during respiration were studied to assess the potential of radiotherapy gated to respiration to minimize normal tissue irradiation. Twelve patients with mediastinal Hodgkins disease were assessed using chest radiographs and thoracic computed tomography (CT) scans both during quiet breathing and at maximum inspiration in the standing, supine, and prone positions. A simple measure of the bulk of mediastinal disease, the ratio of the width of mediastinal mass to thoracic diameter, was determined from posteroanterior (PA) chest radiographs. The volumes of mediastinum, irradiated and protected lung if anteroposterior (AP) and PA mantle fields were used were determined from sequential thoracic CT scans and three‐dimensional treatment planning and compared at quiet breathing and deep inspiration. The mediastinal width to thoracic diameter ratio decreased from quiet breathing to deep inspiration an average of 3%, 9%, and 11% for the standing, supine, and prone positions, respectively. Lung volumes as measured from the thoracic CT scans showed that on average, 8% more lung was protected at deep inspiration than at quiet breathing, independent of treatment position. The maximum increase in the percentage of protected lung from quiet breathing to deep inspiration was seen in patients with extensive mediastinal adenopathy suggesting that radiotherapy gated to respiration may be most advantageous in the subset of patients.

Potential for improvement in radiation therapy

A successful strategy for improving the efficacy of radiation therapy has been to improve dose distribution, that is, reduce treatment volume toward target volume. This is so as the smaller treatment volume has permitted a higher dose to the target (hence a high tumor control probability) and a lesser volume of non-target tissues being irradiated (consequently a reduced frequency and severity of treatment related morbidity). There are in place several important means for further improvements in dose distributions. These include: (a) 3D graphic reconstruction of the affected part with definition of the position of the tumor vis-a-vis the adjacent normal structures; (b) explicit inclusion in the treatment plan of the uncertainty band around each isodose contour; (c) on-line contrast enhanced visual monitoring of the target tissue during the individual treatment session; (d) gating of treatment so as to reduce the impact of patient motion on the needed treatment volume; (e) use of computer control systems to execute the treatment; and (f) use of treatment methods which achieve a reduced treatment volume. In an examination for sites for which treatment volumes might be decreased by a substantial factor we have compared treatment volumes for radical surgical and radiation therapy. Results are presented for carcinomas of the cervix (Stage IB), breast (Stage II), floor of mouth (Stage II). We describe a system developed here for on-line visual monitoring of the tissues covered by the treatment field. Brief descriptions are given of results of low LET charged particle radiation therapy and of intraoperative electron beam therapy. Also, the program developed here to use computer graphic techniques to display tumor and normal structures and isodose countours with uncertainty bands around each contour is mentioned.

pS2 expression in primary breast carcinomas: Relationship to clinical and histological features and survival

SummarypS2 protein expression has been reported to have prognostic significance in human breast carcinomas and to correlate with estrogen receptor positivity, although these findings have not been confirmed by all investigators. pS2 positivity was compared to various clinical and histologic parameters in a retrospective study of 290 patients (median follow-up 7.2 years) and significantly correlated with tumor grade and estrogen receptor content (p=0.001 and p=0.0007, respectively). Significant associations between pS2 positivity and lymph node metastases, T stage, histologic tumor type, and patient age were not observed. Univariate and multivariate analyses (controlling for estrogen receptor content, T and N stage) of the patient population at large showed that pS2 positivity was not predictive of disease-free or overall survival. Univariate analysis of lymph node negative patients demonstrated that both pS2 and estrogen receptor positivity were significantly associated with a better outcome. Multivariate analysis of these patients, however, showed that only estrogen receptor data had independent prognostic significance. This study suggests that immunohistochemical analysis for pS2 protein expression will not contribute additional prognostic information if the estrogen receptor content is known.

Visualization of internal motion within a treatment portal duringa radiation therapy treatment

We offer a method for visualization of treatment portals continually during a radiation therapy treatment. Using digital image processing in conjunction with a fluorescent screen, portal images are obtained almost instantly. Images of quality that are clinically useful can be visualized every second. Digital enhancement further improves the quality of the images. The availability of instant portal images before each treatment can be most helpful in verifying that the patient is correctly and precisely set up prior to the onset of radiation. The ability to visualize treatment portals continuously during a treatment can help to ensure that radiation is restricted to the prescribed field and is not altered significantly by patient motion. In this report, we show and discuss a sequence of instant portal images obtained during a single treatment in which motion and absence of motion of internal anatomy is clearly demonstrated.

Radiation-blocking shields to localize periarticular radiation precisely for prevention of heterotopic bone formation around uncemented total hip arthroplasties

Sixteen patients (18 hips) were treated with localized radiation therapy limited to periarticular regions surrounding the femoral neck by shielding the prosthesis and the adjacent regions to prevent heterotopic bone formation around the uncemented prosthesis. All hips received 1500 rads. Eight of these hips were irradiated after excising severe heterotopic bone, five because they developed extensive heterotopic ossification in the opposite hip, and five others because they were considered to be at high risk for developing heterotopic ossification. Only two of the 18 hips developed a small amount of heterotopic bone after localized periarticular radiation. All wounds healed primarily. No progressive radiolucencies developed at the bone-prosthesis interface. There was only one trochanteric nonunion of six trochanteric osteotomies. Localized periarticular radiation therapy with precision shielding of the prosthetic components and adjacent skeletal structures is an effective means to prevent heterotopic bone formation around cementless total hip arthroplasties. It also has the advantage of not adversely affecting the healing of the trochanteric osteotomy.

Stage IA to IIB mediastinal Hodgkin's disease: three-dimensional volumetric assessment of response to treatment.

From 1979 to 1986, the response to treatment of 53 patients with stage IA to IIB mediastinal Hodgkins disease was evaluated by three-dimensional volumetric analysis using thoracic computed tomographic (CT) scans. The mean initial volume of mediastinal disease in 34 patients treated with mantle and para-aortic irradiation was 166 mL, whereas for 19 patients treated with two to six cycles of multiagent chemotherapy and mantle and para-aortic irradiation the mean initial volume was 446 mL. Preliminary data suggested that patients with mediastinal volumes of less than 200 mL had a lower mediastinal relapse rate (13%) than patients with volumes greater than 200 mL (32%). For 12 patients receiving six cycles of nitrogen mustard, vincristine, procarbazine, and prednisone (MOPP), those with a greater than 85% reduction in volume 1 to 2 months after chemotherapy had a lower incidence of mediastinal relapse (zero of six, 0%) compared with patients having 85% or less reduction in volume (four of six, 67%). The primary value of this technique is that it provides a sensitive assessment of response to treatment and may aid in monitoring the effectiveness of a given treatment.

Three-dimensional volumetric assessment of response to treatment: Stage I and II diffuse large cell lymphoma of the mediastinum

From 1981 to 1986, 12 patients with Stage I and II diffuse large cell lymphoma of the mediastinum were treated with 4 or more cycles of multiagent chemotherapy and for nine patients this was followed by mediastinal irradiation. The response to treatment was assessed by three-dimensional volumetric analysis utilizing thoracic CT scans. The initial mean tumor volume of the five patients relapsing was 540 ml in contrast to an initial mean tumor volume of 360 ml for the seven patients remaining in remission. Of the eight patients in whom mediastinal lymphoma volumes could be assessed 1-2 months after chemotherapy prior to mediastinal irradiation, the three patients who have relapsed had volumes of 292, 92, and 50 ml (mean volume 145 ml) in contrast to five patients who have remained in remission with residual volume abnormalities of 4-87 ml (mean volume 32 ml). Four patients in prolonged remission with CT scans taken one year after treatment have been noted to have mediastinal tumor volumes of 0-28 ml with a mean value of 10 ml. This volumetric technique to assess the extent of mediastinal large cell lymphoma from thoracic CT scans appears to be a useful method to quantitate the amount of disease at presentation as well as objectively monitor response to treatment.