Colorectal cancer: metastatic patterns and prognosis.

From 1979 to 1982, 163 patients with colorectal cancer were found to have distant metastases. Of these, 112 (69%) had metastatic disease at the time of initial diagnosis (synchronous metastases [SM]); in the remaining 51 (31%) metastases developed during the course of the disease (metachronous metastases [MM]). The liver was the most common site of metastasis in both groups (72% and 65%, respectively); with the exception of brain metastasis, liver metastasis had the worst prognosis (median survival time [MST], 9 months). The MST for other sites of metastasis were: lung, 10.5 months; bone, 10 months; multiple sites, 10 months; and brain, 5.5 months. Of the 81 patients with SM in the liver, 38% were treated with single modality therapy and 62% with combined modality therapy. Thirty-three patients had MM in the liver. The median time for development of liver metastases (metastasis-free interval [MFI]) was 17.5 months; only lung metastases developed faster (12 months). MFIs for other sites were 20, 20.5, and 33 months for bone, multiple sites, and brain, respectively.

Breast cancer: metastatic patterns and their prognosis.

From 1969 to 1977, metastatic disease developed in 145 of the 558 patients treated for breast cancer at the University of Maryland Medical System. The most common first site of distant spread was bone (51%), followed by lung (17%), brain (16%), and liver (6%). The remaining 10% of patients had multiple metastatic sites. Fewer than 10% of the entire group received adjuvant chemotherapy after primary treatment. When metastatic disease appeared, most patients had palliative systemic chemotherapy and/or irradiation. In general, patients with initially negative axillary nodes had a longer median time until relapse (development of metastatic disease) and a longer survival time after diagnosis of metastases than patients with initially positive nodes. Liver was the least common initial metastatic site; while liver metastasis was seen only in patients with positive axillary nodes, it carried the worst prognosis. The overall median survival time after metastasis was 12 months for bone and lung lesions, three months for brain lesions, and only one month for liver metastasis. The median survival of patients with multiple metastatic sites was 7.5 months. No correlation was found between time until relapse and survival after metastasis. Patients in whom distant metastases developed relatively soon after the initial diagnosis had the same postmetastatic prognosis as patients whose disease metastasized later. No correlation was found between age at initial diagnosis and metastasis-free interval or survival after metastasis.

A phase I/II trial of whole-abdominal plus pelvic irradiation for Astler-Coller stage beta 2, C colorectal cancer.

From 1982 to 1986, after radical surgery (S) for carcinoma of the rectum and rectosigmoid colon, 25 consecutive patients were entered into a Phase I/II study exploring adjuvant radiation (RT). The latter was given with a single fraction of whole abdomen (mid-body) irradiation (MBI), followed by conventional whole pelvis irradiation (WPI). The minimum follow-up time was 12 months, and the maximum was 44 months. There was escalation of the single MBI dose: 5 Gy in 11 patients, 6 Gy in two patients, and 8 Gy in 10 patients. The 2-year survival rate has been 100 and 45% for Stages B2 and C patients. Only 1/7 Astler-Coller Stage B2 patients failed; this failure was in the lungs. Seven of 15 patients with Stage C failed: one locally, three in the liver, and three in the lungs. Single MBI doses greater than 5 Gy have yielded a high incidence of intestinal obstruction when combined with routine WPI. Consequently, this combination requires both some modification and careful attention if used in future trials exploring new treatment approaches for colorectal cancer.

Cancer of uterine cervix stage IB. Treatment results and prognostic factors.

From 1969 through 1977, 210 patients with Stage IB carcinoma of the uterine cervix were treated at University of Maryland Hospital. Fifty-six patients were treated by radical hysterectomy (S), 136 patients were treated by a full course of radiation therapy (RT) only and 18 patients received radiation treatment following radical surgery (S + RT). The 5-year determinate survival rates were almost the same in the S group and RT alone group (79% and 77%, respectively). The 5-year determinate survival rate in the S + RT group was 50%, which was statistical significantly lower than S alone or RT alone groups (P less than 0.05). Several prognostic factors were analyzed in the radiated patients: the size of the primary lesion, location of the lesion within the cervix, tumor grade, age of the patients at the time of diagnosis, and complete blood count nadir during the course of radiation treatment. The only factor found to influence the prognosis was the size of the primary tumor. The patients with smaller tumors had a better prognosis; the absolute and determinate 5-year survival rates were 80% and 82%, while the absolute and determinate survival rates in the large, fungating tumor replacing the entire cervix were 56% and 60%, respectively (P less than 0.001). The complication rate was 22% in the RT alone, 22% in the S + RT, and 25% in the S alone groups.

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.

What can be expected when radiation therapy becomes the only curative alternative for endometrial cancer?

Fifty-four patients with endometrial carcinoma were treated by radiation alone between 1962 and 1977, because of severe associated medical problems that contraindicated surgery. The overall 5-year absolute and determinate survival rates were 46% and 54%, respectively. The majority of patients who presented with Stage I, grade I disease were treated with only intracavitary radiation; this yielded a 75% 5-year survival rate. However, the combination of external and intracavitary radiation achieved the best results in the overall group. The stage of the disease, grade, age at diagnosis, and treatment techniques correlated well with failure rates. However, only the tumor grade and treatment techniques influenced failure patterns. The length of the uterine cavity did not have any prognostic influence in these patients.

Radiation therapy in primary carcinoma of the female urethra. II. An update on results.

Analysis of 21 patients with primary carcinoma of the female urethra who were treated by radiation only, from 1961 to 1980, is presented. Of 21 patients studied, 14 were treated for curative intent, 6 for palliation, and 1 patient did not finish the treatment as planned. For the curative group, radiation treatment was highly individualized and integrated with a special interest in brachytherapy. The authors were able to obtain excellent local control and subsequent 5-year-disease-free survival in Stage I, II, IIIA, IIIB, IIIC, and IV. The overall local control was 11 of 14 (78%) while achieving 77% 5-year disease-free survival. The bladder neck involvement continues to be a therapeutic problem and represents the only failure site. Factors responsible for the prognosis of this cancer are the extent of the cancer (clinical stage), location, individualization, and integration of the external beam and brachytherapy. Involvement of the vulva or vagina did not alter the good outcome, but involvement of the bladder neck, bladder, parametrium, and inguinal node represented a poor prognosis. Palliative irradiation treatment for those whose diseases were beyond cure can only offer a short-term, symptom-free result in 70% (5 of 7) of cases treated. No major complications occurred as a consequence of radiation treatment. Sample cases, particularly with brachytherapy and dosimetric analysis, are discussed.

Prognosticators in recurrent breast cancer. A 15-year experience with irradiation.

After initial surgery, 133 breast cancer patients, who did not receive postoperative radiation or chemotherapy, were subsequently irradiated for recurrences in the Department of Radiation Oncology, University of Maryland Hospital. All patients have been followed for a minimum of 5 years after the treatment of recurrences. An extensive analysis was done in search of prognosticators for outcome in recurrent breast cancer. Traditional prognostic factors, such as the initial axillary status, primary surgical procedure, initial menopausal status, time and site of recurrences, distant metastases and radiation dose and field issues, were investigated. No correlation was found between the initial axillary status and the overall prognosis after recurrence. The main prognosticators were: the size of the initial breast tumor, the radiation treatment for recurrences, and the presence of, or time to, distant metastases. Initial T1-T2 breast tumors were associated with a delayed onset of recurrences and a lower incidence of chest wall relapses; in turn, both the latter situations yielded the best outcome. Radiation doses of more than 4000 rad in 4 weeks delivered with locoregional fields achieved a local control rate of 72%, and the best 5-year post-recurrence survival (57%). In 52% of the recurrent breast cancer patients, distant metastases were discovered; 70% of them occurred within 2 years from recurrence. The overall post-recurrence 5-year survival for the entire series was 40%. Both the results achieved with radiation therapy and the need for a logical strategy to approach the problem of breast cancer recurrences are discussed. The situation for a large proportion of these patients is not hopeless, and many are salvagable . Combined modality approaches could offer the best possibilities of survival. However, the importance of radiation therapy in the management of these patients cannot be denied or ignored.

Radium needles implant in the treatment of extensive vaginal involvement from cervical carcinoma. A dosimetry appraisal.

An appraisal of the dosimetry of a modified brachytherapy approach is presented for improving the local control of extensive vaginal involvement from carcinoma of the cervix. This approach incorporates radium needles implant to the vaginal disease in conjunction with the usual routine intracavitary radium application. The aim of the interstitial implant is specifically to supplement the dose to the vaginal disease from the intracavitary application. Our procedure for accomplishing this boost in the dose to the vagina depends on the location, extent and thickness of the vaginal lesion following external beam irradiation of the whole pelvis. An increase of greater than 50 per cent in the dose to the vaginal disease is gained by this combination intracavitary/implant approach which has been used in a variety of cases covering virtually all pertinent stages of cervical carcinoma. Discussion of the dosimetry of example cases is presented to demonstrate the value of combining interstitial and intracavitary therapy for this specific clinical application.

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.

Radiation treatment of carcinoma of the cervix with extension into the endometrium: a reappraisal of its significance.

During the period from 1969--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, 82 patients were identified as having D & C positive for squamous cell cancer present in the curettings with or without endometrial tissue. Clinical staging was done using FIGO guidelines and the treatment of endometrial extension was the same as with regular cervical cancer. Of 82 cases who are eligible for a minimum five-year follow-up, the absolute five-year survival is as follows: Stage I, 68%, (17/25); Stage II, 62% (18/29); Stage III, 40% (10/25); Stage IV, 0% (0/3). The most interesting features are the local and distant failures in Stage I and II disease. Local failure in Stage I and II in this study is in line with other series. Distant metastasis, however, occurs at the rate of 20% in Stage I between 1--2 years after treatment (as compared to the control of 5%). In Stage II, the distant disease increases to 24% with a substantial number of local failure with distant metastasis. Based on our findings and others, it seems appropriate to suggest D &nd C be done routinely in order to identify the extension of cancer into the endometrium and treat them properly. Also it appears appropriate to re-examine our policy of the treatment to minimize both local and distant failures with suggestions outlined in Schema I and II along with possibility of a future chemotherapeutic management to minimize the distant disease.

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.

Influence of treatment and tumor grade on the prognosis of stage II carcinoma of the endometrium.

A retrospective analysis of 53 patients with stage II endometrial carcinoma treated between 1963 and 1975 was undertaken to evaluate the efficacy of treatment methods and the effect of tumor grade on survival and failure. Thirty-eight patients were irradiated preoperatively followed by total abdominal hysterectomy and bilateral salpingo-oophorectomy, 15 were followed for at least 5 years with no lost to follow-up. An overall 5-year disease-free survival of 60.6 per cent was obtained. Further analysis of the data showed that tumor grade and treatment method were important factors influencing the prognosis. The data support the improved survival rate when irradiation is followed by hysterectomy. Patients with a low grade tumor (G1) given preoperative irradiation have a better survival than those with high grade tumor (G3) treated by the same method. Failure rate is also dependent on method of treatment and tumor grade. The results are in agreement with several data in the literature that combination of the irradiation and surgery should be the treatment of choice for stage II endometrial carcinoma. Tumor grade is also an important factor and must be evaluated for the extension of the disease before the proper management. For the high grade tumor, para-aortic node sampling might be important for the irradiation and should warrant further investigation.

Parametrial implants in the treatment of stage IIIB carcinoma of the cervix. II. Analysis of success and failure.

Local failure (in the cervix and pelvic wall) continues to be a major reason for poor results following conventional radiation treatment of Stage IIIB (FIGO) carcinoma of the cervix. Attempting to minimize this local failure, in 1975 and early 1976, the Radiation Therapy Department, University of Maryland Hospital, began using a parametrial implant technique in a selected group of patients who had met the criteria for implant in Stage IIIB carcinoma of the cervix. Essentially, prior to radium implant, all patients received whole-pelvis irradiation (4000-5000 rad TP/four to five weeks) plus an appropriate parametrial boost to the affected side (pelvic wall to 5500 rad/over five and a half weeks). Two types of radium were given: 1) a protruding tandem with parametrial implant by means of radium needles; and 2) a radium implant to the lower segment of uterus and affected parametrium plus a vaginal colpostat in cases of severe shortening (or absence) of the uterine cavity or when we were unable to identify the uterine cavity. A total of 31 cases were treated with one or the other of these techniques and have been followed for a minimum of three years. Results show an absolute disease-free survival rate of 64.5% (20 of 31) with a determinate disease-free survival rate of 71.4% (20 of 28). The overall local control rate is 84% (26 of 31). Analysis of local and paraaortic failures as well as distant metastases and complications are presented in detail.

Radiation management of carcinoma of the cervical stump.

In spite of a low incidence of carcinoma of the cervical stump at the present time, the management of this interesting disease deserves special attention because of the success which can be obtained with proper treatment. We have reviewed our cervical stump cases treated at the University of Maryland Hospital, Department of Radiation Therapy, from 1962 to 1973. Of 107 cases treated, only 100 cases were "true cases" of carcinoma of the stump and were eligible for this study. 7 cases were excluded from the study because they were probably coincidental carcinomas and were treated soon after subtotal hysterectomy. The lesions were staged according to the FIGO system. 93 cases (93%) were invasive squamous cell carcinoma, 6 cases (6%) adenocarcinoma and 1 case (1%) transitional cell carcinoma. Of 100 cases with a minimum 5 year follow-up, the absolute 5-year cure rate for various clinical stages is as follows: Stage I 83.3% (20/24); Stage IIA 75.0% (9/12); Stage IIB 62.5% (20/32); Stage IIIA 50% (1/2); Stage IIIB 48% (12/25); Stage IV 20% (1/5). The overall absolute 5-year cure rate for all stages combined is 63% (63/100) compatible with a series reported by M.D. Anderson. A better result in Stage IIIB as compared to several previous reports is thought to be due to extensive and aggressive interstitial radium therapy properly combined with external supervoltage irradiation. Techniques of treatment stage by stage including computerized dosimetry will be discussed along with complications and failures.