Wilfred Sewchand

The influence of patients' age and tumor grade on the prognosis of carcinoma of the cervix.

Many factors can influence the prognosis of cancer of the cervix. They range from clinical staging, various histologic cell types, to extensions into the endometrium. Very little is known about the influence of the patients‐ age and constitutional status of the host (patient) on the prognosis of cervical cancer. Over the past several years, we have been observing that when cancer of the cervix occurs in the relatively young patient, they tend to be more aggressive and inspite of the usual accepted treatment, the majority of them do not survive their disease. From 1969 to 1974, 561 patients with proven invasive squamous cell carcinoma of the cervix were treated by irradiation only in the Department of Radiation Therapy, University of Maryland Hospital. Of these, 94 patients were studied and their ages ranged from 23 to 39 years. They were staged following FIGO guidelines and subject to the usual irradiation treatment for cervical cancer. All patients are eligible for a minimum five‐year follow‐up and the absolute five‐year disease‐free survival is as follows: Stage I, 70.2%, (33/47); Stage II, 54%, (14/26); Stage III, 17%, (3/18) and Stage IV, 0%, (0/3). One of the most interesting features observed in Stage I and II disease is distant disease; 26% for Stage I and 42% for Stage II. Further analysis of our result for Stage I and II shows that tumor grading may be responsible for poor outcome. Three Grade systems were used for the study and the result clearly shows that Grade III or poorly differentiated squamous cell carcinoma had the poorest five‐year survival; for example, survival for Stage I disease is 43% and 44% for Stage II. Analysis of the failures following the treatment suggests that about 50% of patients with Grade III disease have already had distant disease by the time the diagnosis was made. Recommendations for futher appropriate treatment is suggested.

A prospective randomized trial comparing once-a-week vs daily radiation therapy for locally-advanced, non-metastatic, lung cancer: A preliminary report☆

This is the first report of an on-going Phase III protocol for patients with locally-advanced, non-metastatic, measurable lung cancer. The study randomizes two arms: 6000 rad using 500 rad fractions once a week (1 X W) for 12 weeks with spinal cord (SC) protection at 3000 rad; and 6000 rad using 200 rad fractions daily (5 X W) for 6 weeks with SC protection at 4500 rad. Both arms use an initially large loco-regional field that is further reduced when tumor doses reach 3000 rad in (1 X W) arm and 5000 rad in (5 X W) arm. The protocol was activated April 1982; as of August 1984, it had accrued 100 patients of whom 68 were evaluable [29 (1 X W) and 39 (5 X W)]. There have been no major differences in tumor responses or failure patterns between the (1 X W) and (5 X W) arms; response rates have been 69 and 64%; CR 31 and 20%; total incidence of local failures 20 and 23%; and overall incidence of distant failures 34 and 43%, respectively. The (1 X W) arm has been far better tolerated with 76% of its patients free of any esophagitis and 97% without weight loss, as compared to only 33 and 67% in the (5 X W), respectively. The (1 X W) arm has not conveyed loss in tumor control effectiveness, in-treatment progression, or higher incidence of distant spread. Subacute and chronic complications have been minimal with either treatment. No fatal or life-threatening toxicities have occurred; the incidence of severe complications has been 7% in the (1 X W) arm and 8% in the (5 X W) arm. Nevertheless, the number of patients alive and at risk greater than or equal to 12 months is still relatively small; definitive statements regarding very late toxic reactions cannot yet be made. Compared to their protocyptes [a (1 X W) Pilot Study and the 6000 rad/6 weeks arm of RTOG Protocol 73-01], results in the present protocol arms have not been different from what was expected. Once a week RT yields results that appear no different from those achieved with conventional RT in lung cancer.

Once-a-week vs conventional daily radiation treatment for lung cancer: Final report

This is the final report of a prospective randomized clinical trial which began in 1982 and explored once-a-week hypofractionation in lung cancer patients with unresectable, non-metastatic, measurable, loco-regionally advanced disease. Stratification to this protocol has been done by histology, stage, and performance status categories. Patients with ipsilateral supraclavicular and/or brain metastases as the only evidence of distant spread, have been included in the study, but were stratified and analyzed separately. The two protocol arms were: (I) Conventional daily radiation [5 x W]-5 daily fractions of 2 Gy each to a total dose of 60 Gy in 6 weeks, protecting the spinal (SC) at 45 Gy and (II) Once-a-week radiation [1 x W]-one weekly fraction of 5 Gy each to a total tumor dose of 60 Gy in 12 weeks protecting the SC at 30 Gy. A total of 150 patients have been entered. Of these, 30 pts. are inevaluable, but the reasons of non-compliance, progression of disease or death due to intercurrent disease were of equal incidence in both groups. Of the 120 evaluable patients, 63 were treated 5 x W and 57 with 1 x W therapy. Complete tumor responses are similar in both arms with 1 x W pts demonstrating a numerical advantage (26% vs 17%). The average follow-up of the entire series is 3 yrs with a range of 12-66 months. Survival data is comparable in both groups with the 12 and 24 month actuarial survival of 49% and 23% for the 5 x W arm and 59% and 29% for the 1 x W arm. 1 x W patients continue to show a better tolerance than 5 x W pts. There are sufficient long-term survivors in both arms to assess chronic toxicity. The number of patients alive at 12, 18, and 24 months were 25, 11, and 5 for the 5 x W arm and 29, 16, and 7 for the 1 x W arm. No significant differences in late reactions have been noted. The longest surviving patient in the 1 x W arm is now 48 months after treatment.

Radiation management of advanced nasopharyngeal cancer

During the period from 1957–1976, 70 patients with advanced malignant tumors of nasopharynx were treated by irradiation in the Department of Radiation Therapy, University of Maryland Hospital. Fortynine patients were treated with curative intent and 21 patients with palliative purpose. Of 49 patients treated for cure, 22 (45%) survived disease‐free for at least 5 years. Local control was achieved best (92%) by combined treatment, external beam and brachytherapy. Factors responsible for local control and disease‐free survival, appear to be related to clinical staging (primary and nodal disease), cell types and treatment used. In spite of aggressive radiation treatment for advanced cases (Stages III and IV), distant disease is still a major problem and will necessitate further trial by combined chemotherapeutic treatment with irradiation. This article highlights the results and failures of the technique of the irradiation, both external and brachytherapy. It is suggested that aggressive radiation treatment using a combined approach (external beam and brachytherapy, whenever possible) be done in all cases for cure. Palliative treatment can only offer a short‐term symptom‐free status in 72% of all cases treated.

Adenocarcinoma arising in female urethral diverticulum

Cancer arising from a female urethral diverticulum is rare, and because of its rarity, a review of the medical literature reveals significant nonuniformity in its management. We report an additional 2 cases of this disease, one of which has an even rarer feature of being mucin-producing. The management of our 2 cases is presented in detail and in line with the management of female urethral cancer. From our extensive literature search, diverticulectomy alone showed poor results with the highest rate of recurrence (67%). Extensive surgery, either in the form of cystourethrectomy or anterior exenteration, offered results comparable with those of combined therapy (diverticulectomy and full course of irradiation for early cases; preoperative irradiation followed by cystourethrectomy for late cases). Individualization of radiation treatment and cooperative effort between urologist and radiation oncologist are essential if best results are to be achieved.

Value of multi-planar CT images in interactive dosimetry planning of intracavitary therapy

A method of intracavitary treatment planning and dosimetry analysis which uses multi-planar reconstructed computerized tomography (CT) images is presented. The aim of the method is to improve ability to precisely locate clinical reference points, to fully define pertinent anatomic structures and to provide dose distributions and their relationship to these structures in multiple planes. Our approach is based on interactive treatment planning and point dose display on sagittal and coronal reconstructed CT images as well as the usual transaxial image. The advantages of clinical evaluation of isodoses directly on multi-planar CT images are assessed. These include precise anatomic and dose relationships between the cervix and paracervical structures, the bladder, rectum and pelvic node-bearing sites. Problems of image magnification, blurred images and inadequate resolution attendant to orthogonal radiographs, which are the basis of current techniques, are minimal. Analysis and results of the method and a comparison with the technique of orthogonal radiographs are presented for a demonstration case.

Technique and preliminary results of interstitial irradiation for primary brain tumors

We have conducted a phase-I clinical trial of CT guided stereotactic implantation of Ir192 in the treatment of malignant astrocytomas. During the past year, 16 patients have been implanted with two to four catheters in the residual enhancing portion of their tumor. These patients represent 50% of our total experience with the CT compatible Leksell frame. Each catheter contains three to six high intensity (2.0 to 2.5 mg Ra equivalent) seeds with 0.5 cm separation between the sources. The total activity of Ir192 per implant has been 30–65 mg radium equivalent. In the 16 patients, 49 catheters have been placed, an average of three targets calculated per patient and no targets have been missed. The radiation exposure to personnel has been surveyed in detail and drops off to less than 2 mr/h six feet from the patient when our custombuilt radiation shield is employed. We have reserved permanent implantation of I125 for patients with tumors in unusual locations (e.g. pineal) or for individuals with slowly growing non-gliomatous lesions (i.e. meningioma). The tumor volumes have ranged from 12–120 cm3. Unique aspects of our implant procedure include the use of a Leksell frame already adapted to the GE-8800 scanner, the use of pre- and post-implant computerized treatment planning programs to determine the dose distribution profiles and the use of adjustable metal collars crimped to the outer catheters to provide ease of insertion, uniform pre-implant catheter length, and protection against source migration. Two of our patients have suffered from subacute radiation reactions, primarily due to delayed cerebral edema and both of these cases have largely resolved. We believe that it is technologically feasible to deliver 5000 rads to the tumor periphery in 50 h without undue patient toxicity or environmental radiation hazard. The system we have been studying is fully compatible with the simultaneous use of mechanical cytoreduction, chemotherapy and interstitial hyperthermia.

Carcinoma of the floor of the mouth: a 20-year experience

From 1955 to 1975, 116 patients with squamous cell carcinoma of the floor of the mouth were primarily treated by irradiation in the Department of Radiation Oncology, University of Maryland at Baltimore. Of these, 93 evaluable patients yielded loco-regional control rates of 83, 85, 42 and 21% for Stages I-IV, respectively. A palisading technique of radium needle implants was used, either alone or combined with external beam therapy, for early tumors (Stages I-II). Similar control rates were achieved by these two techniques: 13/14 for interstitial irradiation alone and 16/24 for combined interstitial and external irradiation. In selected early cases (Stages I-II), errors in staging were minimized by the systematic use of a needle biopsy of the submaxillary triangle for suspicious submaxillary swellings. Patients with early lesions and truly negative nodes (N0) only received irradiation to the primary tumor bed. No subsequent nodal neck failures have occurred in 13 of such patients. The overall complication rate for the entire series was 17% with only 8 patients requiring surgery. No differences in complication rates were found among the treatment modalities employed. The distribution of lymph nodal involvement by anatomical level, correlation of histological differentiation or tumor aggressiveness at presentation, the dosimetric analysis of the palisading interstitial technique, the spread and failure patterns and other observations are discussed.

Single dose total lymphoid irradiation combined with cyclophosphamide as immunosuppression for human marrow transplantation in aplastic anemia

Abstract Six patients with aplastic anemia underwent bone marrow transplantation following conditioning with high dose cyclophosphamide and single dose total lymphoid irradiation with 750 rad, 26 rad/min at the midplane of the patient. They all received bone marrow from human leukocyte antigens/mixed lymphocyte culture (HLA/MLC) matched siblings. Five of 6 patients were alive without complications at 12, 11, 7, 4 and 4 months respectively. The remaining patient died from sepsis which he had prior to transplantation. There were no graft rejection, graft-vs-Host Disease (GVHD) or interstitial pneumonitis among these patients. The procedure was well tolerated with minimal side effects. The results will be compared with those of groups whose bone marrow was previously transplanted with different immunosuppressive methods.

Palliative half-body irradiation: Single and fractionated doses

SYSTEMIC HALF-BODY IRRADIATION (HBI) has been used extensively for the palliation of cancer pain. It has also been tried as an adjuvant therapy in patients with advanced locoregional tumors with a high propensity to disseminate and as consolidation therapy after primary systemic treatment. The limitations and toxicity of this technique have been studied extensively. Single doses of 600 rad to the upper half-body (UHB) and 800 rad to the lower half-body (LBH) have been found to achieve excellent palliative responses with an acceptable rate of complications.In order to determine the feasibility of increasing the dose of radiation delivered, a pilot study was conducted at the University of Maryland. Forty-four patients received palliative HBI. Of these, the first 36 patients received single doses to the UHB, mid-body (MB), or LHB using doses of 600 rad to the UHB and 800 rad to MB and LHB. The last consecutive eight patients received two fractions of 400 rad each, given 2–3 weeks apart.The pain response achieved by each group is similar; single dose achieved 84% complete and partial responses vs. the fractionated group, which achieved 87% complete and partial responses. The main difference between the two groups was the time necessary to achieve a response. The single dose group achieved improvement of their symptoms in 24–48 hours in approximately 70% of the patients who responded. The fractionated group achieved symptomatic response after the second dose of irradiation was given.The toxicity of both groups was similar. The acute radiation syndrome after half-body irradiation was controlled with a premedication program. Hematological toxicity was similar in both groups, and no cases of fatal radiation pneumonitis were seen. At the present time, it seems feasible to proceed with other fractionation schemes in order to try to increase the total dose delivered.