Natural History and Management of Isolated Local-Regional Recurrence Following Mastectomy.

The average incidence of isolated local-regional recurrence following modified radical mastectomy is 10% to 20%, but it can be as low as 5% or as high as 40%, depending on the presence or absence of various risk factors. One of the objectives of this article is to discuss how to evaluate the risk of locoregional failure. In addition, although the average overall survival rate following recurrence is approximately 40% at 5 years and 25% at 10 years, individual patient survival varies considerably and depends on a number of fairly well-documented prognostic features that are also discussed here. The unfortunate reality is that control of an isolated local-regional recurrence for the duration of life is not frequently achieved. Even with optimal irradiation, 50% of all patients will die with uncontrolled local-regional disease. The quality of life for patients with uncontrolled disease is often very poor, and some examples are shown here. For this reason, local-regional recurrence should be avoided. The way to avoid (or at least minimize) local-regional recurrence is to give postoperative irradiation to those who are at high risk for local-regional recurrence following mastectomy. This author considers the risk to be "high" when it reaches 25% to 30%.

Breast conserving surgery and irradiation: the importance of demarcating the excision cavity with surgical clips.

PURPOSE: To determine whether or not the surgical scar and surgical induration are suitable landmarks for localizing the boost field in the treatment of patients undergoing breast conservation surgery and irradiation. METHODS AND MATERIALS: Thirty-five patients had surgical clips placed in the excision cavity at the time of tumor excision. The boost field locations for these patients were determined by encompassing the surgical induration with a minimum 2 cm margin or, when there was no induration, by encompassing the incision scar with a 3 cm margin. Simulator radiographs were taken with the boost field margins marked with solder wire. RESULTS: The simulator radiographs showed that the excision cavity clips were at or outside the boost field margins in 19 patients, 54% of the entire group. An unexpected finding was that, in six of the 23 patients with the surgical scar 2 cm medial or lateral to the areola, the excision cavity clips were inadequately covered by tangential fields even though the fields appeared to be adequate based on external landmarks. CONCLUSION: (a) This study suggests that the skin incision and surgical induration are not reliable landmarks for boost field localization. (b) Without surgical clips, part of the excision cavity would have underdosed by the tangential fields in 23% of patients with medial or lateral surgical scars.

The use of high dose rate endobronchial brachytherapy to palliate symptomatic endobronchial recurrence of previously irradiated bronchogenic carcinoma.

Thirty-eight patients were treated with high dose rate endobronchial brachytherapy to palliate symptoms (cough, hemoptysis, fever, and/or shortness of breath) caused by endobronchial of previously irradiated (greater than or equal to 5000 cGy) bronchogenic carcinoma. The dose per fraction was 600 cGy at a radius of 1 cm from the center of the linear path of the source, and each patient received three fraction, each fraction separated by a 1-week interval. Twenty-nine patients (76%) had symptomatic improvement, 16 with complete and 13 with partial relief of symptoms. The likelihood of symptom relief was greater in those patients who had extra-bronchial tumor measuring less than 5 cm (15/15) compared to those with extra-bronchial tumor measuring greater than or equal to 5 cm (2/8). The median duration of symptom relief was 7.5 months. Repeat bronchoscopy done 3 months after brachytherapy revealed that 41% (11/27) had complete tumor regression and another 41% (11/27) had partial regression. Nine of 14 patients with post-obstructive atelectasis/pneumonitis had radiographic improvement. Twelve patients (32%) died from massive hemoptysis occurring 2-56 weeks (median 10 weeks) after brachytherapy. Location of the recurrence was the most important predictor of pulmonary hemorrhage. It occurred only in patients with recurrence in the right upper lobe, right mainstem, or left upper lobe bronchus. Whether this high rate of fatal pulmonary hemorrhage was a real phenomenon or a statistical fluke of small numbers remains an unanswered question.

Preoperative planning of breast implants using the breast implant planning device (BIPD).

Interstitial implantation of the tumor excision site is an important component of the treatment program of breast-conserving surgery and irradiation. The currently accepted method of designing and performing the implant in the operating room does not assure adequate coverage of the volume of tissue at risk, i.e., the tissue immediately adjacent to the walls of the original tumor excision cavity. This communication describes a technique of preoperative implant planning that consistently and reliably ensures adequate coverage of the volume of tissue at risk. An integral part of this technique is the use of a new device called the Breast Implant Planning Device. This device is a modification of previously described implant template devices.

Failure patterns in gynecologic cancer.

In reviewing the literature on the patterns of failure in gynecologic malignancies, it is essential to define the type of recurrence resulting from the treatment program pursued. Categorizing them into local recurrences, marginal recurrences, parametrial recurrences, periaortic lymph node recurrences, abdominal recurrences, and distant metastatic disease become an important part in the design of new treatment programs in management. Most recurrences are actually the result of persistent disease. Therefore, the full extent of disease at the time of initial presentation should be determined. Pre-treatment surgical exploration obviously defines more precisely the tumor extent than does clinical stage alone. Samples of retroperitoneal abdominal lymph nodes in cervical, endometrial and ovarian cancer have shown more frequent involvement than previously suspected.

Hysterectomy and adjuvant irradiation for pathologic stage III adenocarcinoma of the endometrium.

Three hundred and four evaluable patients with FIGO clinical Stage I adenocarcinoma of the endometrium were treated with hysterectomy and adjuvant irradiation. At surgery, 15 patients (5%) were found to have disease outside the uterus, but within the pelvis Pathologic Stage III (PSIII). A higher grade of tumor was not associated with an increase in the frequency of PSIII, being 7/158 (4%), 5/89 (6%), and 3/57 (5%) for Grades 1, 2, and 3 respectively. Depth of myometrial invasion correlated with PSIII disease in 5/69 (7%) for less than 1/3 myometrial invasion versus 7/33 (21%) for greater than 1/3 invasion (p = .05). One patient died of intercurrent disease at 4 months with 6/14 (43%) of the remaining patients developing recurrent disease. The site of initial failure was pelvis 1/15 (7%), pelvis and distant metastasis 3/15 (20%), and distant metastasis alone 2/15 (13%). Of seven patients who received external pelvic irradiation, there was one local failure (14%), which is not statistically significant from the 3/8 (38%) local failure rate among patients not receiving external pelvic irradiation (p = .569). None of the seven patients experienced a treatment related complication as a result of adjuvant irradiation.

Treatment of stage I adenocarcinoma of the endometrium by hysterectomy and adjuvant irradiation: a retrospective analysis of 304 patients.

Three hundred and four evaluable patients with FIGO Stage I adenocarcinoma of the endometrium were treated with hysterectomy and irradiation. Irradiation was preoperative in 250 and postoperative in 44 patients. Ten patients had a preoperative implant and postoperative external irradiation. The 5 year actuarial survival was 94%, 80% and 76% for grades 1, 2 and 3, respectively. Within each grade and for all patients there was no difference in survival for Stage IA versus IB. The initial failure rate was 26/304 (9%) with 2% of patients having only a pelvic failure, 2% pelvic and distal failure and 4% a distal failure only. There were four distal vaginal failures and no isolated cuff recurrences. The upper abdomen was the most frequent site of extra-pelvic failure for grade 3, while the periaortic nodes and lung constituted the most common sites of distal failure for grades 1 and 2 tumors. Timing of the hysterectomy following the irradiation was of importance when evaluating the prognostic significance of residual disease or depth of myometrial invasion. The presence of residual disease or greater than 1/3 myometrial invasion had a significantly worse prognosis only among patients who received no preoperative irradiation or who underwent their hysterectomy immediately following a preoperative implant. There was no difference in survival among patients with an initial local failure only as compared to those with an initial distal metastases, as the majority of patients with an initial local failure subsequently developed distant metastases.

Treatment of stage I adenocarcinoma of the endometrium by hysterectomy and irradiation: analysis of complications.

Twelve of 304 patients (4%) treated with surgery and adjuvant irradiation for endometrial carcinoma experienced a serious complication. The complication rate for patients whose irradiation consisted of an implant alone was only 1% (two of 199), if the implant was preoperative, but was 12% (three of 26) if the implant was postoperative. For patients who received external pelvic irradiation as part of their adjuvant therapy, the incidence of complications was 8.8% (seven of 79) and the timing (preoperative versus postoperative) had no effect. There was, however, a significant correlation of the complication rate with an increasing dose of external irradiation to the whole pelvis: For doses of 3000 rad or less, it was 2% (five of 264) but was 18% (seven of 40) for doses in excess of 3000 rad. These data suggest that the safest form of adjuvant irradiation for adenocarcinoma of the endometrium is a preoperative implant, and that adding external pelvic irradiation to the preoperative implant will significantly increase the complication rate if the external dose to the central pelvis exceeds 3000 rad.

Stage I, grade III adenocarcinoma of the endometrium treated with surgery and irradiation. Sites of failure and correlation of failure rate with irradiation technique.

Eighty-three patients treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO) and adjuvant irradiation for Stage I, grade III adenocarcinoma of the endometrium were reviewed. At 5 years, the overall survival was 71%, and the disease-free survival (excluding patients dying of intercurrent disease) was 79%. The failure rates for pelvis alone, pelvis plus distant, and distant alone were 4.8%, 4.8%, and 10.8%, respectively. The most common site of failure was the upper abdomen; 12% of all patients had a failure at this site, either alone or in conjunction with failure at another site. The 24% rate of failure in 50 patients receiving a preoperative implant and external irradiation was not significantly different from the 15% failure rate in 33 patients whose adjuvant irradiation consisted of a preoperative implant only. For the patients who had both an implant and external irradiation, the dose of external irradiation had no correlation with the rate of failure. In contrast, the number of milligram-hours delivered to the uterus by the preoperative implant had a strong inverse correlation with the rate of failure, both for patients receiving an implant only and for those receiving an implant plus external irradiation. The data suggest the following: (1) a high-intensity preoperative uterine implant may be an important adjunct to surgery; and (2) external pelvic irradiation in addition to the implant does not seem to be any more beneficial than an implant alone.

Radiation therapy alone in the treatment of carcinoma of the uterine cervix. II. Analysis of complications.

A retrospective analysis was carried out on 811 patients with histologically proven invasive carcinoma of the uterine cervix treated with irradiation alone. A correlation was made of the doses of irradiation delivered to the pelvic organs with external beam and intracavitary insertions. Approximately 3% of the patients exhibited grade 2 gastrointestinal complications, and 2% developed grade 2 urinary complications; 5% of the patients developed grade 3 gastrointestinal complications, and 3% developed grade 3 urinary complications. Other types of complications, primarily grade 2, such as vaginal necrosis, pelvic abscess, thrombophlebitis, etc, were seen in approximately 5% of the patients. Thus, the total percentage of patients developing grade 2 complications was 10% and grade 3 complications, approximately 8%. About 25% of the patients who had complications showed more than one sequela. The most frequently observed grade 2 complications were proctitis, cystitis, vaginal stenosis, and partial small bowel obstruction which were treated with conservative management. Grade 3 complications required surgical treatment and consisted most frequently of ureteral stricture, vesicovaginal fistula, rectovaginal fistula, sigmoid stricture, small bowel obstruction, proctitis, and large rectal ulcers. The most significant factor affecting the appearance of complications was the total dose of irradiation delivered to the pelvic organs by the whole pelvis external irradiation and intracavitary insertions. With maximum total doses up to 8000 rad the incidence of grade 2 and 3 complications was less than 5%. However, with higher doses the incidence of complications increased to 10% to 15%. In patients receiving total doses of 6000 rad to the bladder or rectum, more complications were noted when only one intracavitary insertion was performed, as compared with two or three. Eighty percent of the rectosigmoid complications occurred within 30 months of initial therapy, in contrast to 48 months for the urinary complications. Patients who developed complications had survival rates comparable to those without complications. This underscores the need to rapidly institute treatment on patients who have severe injury after radiation therapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Adjuvant irradiation for early breast cancer. An on-going controversy.

Adjuvant irradiation has been used in the treatment of breast cancer for over 80 years, but its use has always been, and remains, controversial. It is extremely valuable in the treatment of Stage III and IV breast cancer because of its ability to reduce the local recurrence rate in these late stages down to acceptably low levels; however, to have a significant benefit in Stages I and II, in which the local recurrence rate is only 10% to 20% with mastectomy alone, it should be able to improve survival as well as prevent local recurrence. All of the early trials indicated that adjuvant irradiation neither increased nor decreased survival; however, these trials were flawed by poorly executed randomization processes and/or by the use of radiotherapy that would be considered inadequate by today's standards. The two recent trials, Oslo and Stockholm, which were more stringently randomized and which employed more modern radiotherapy techniques, showed an improved disease-free survival with adjuvant irradiation. Overall, survival, however, was unaffected, save for the small subset of patients with medial tumors and histologically positive axillary nodes. For these patients there was a trend toward survival enhancement by internal mammary node irradiation. All of the trials testing irradiation and surgery against surgery alone have very little relevance in today's adjuvant chemotherapy era; thus, the entire question of survival enhancement by irradiation must be reassessed within the context of adjuvant chemotherapy. Will the combination of adjuvant chemotherapy and irradiation yield a better survival than either adjuvant modality alone? The results of the few prospective trials that have addressed this question are still preliminary, and longer follow-up is necessary before any conclusions can be reached. Also, future studies must be undertaken to address two issues that may be very important when combining chemotherapy and radiotherapy: the sequencing of these two modalities, and the optimum radiotherapy technique for minimizing hematologic suppression.

Local-regional treatment of patients with simultaneous local-regional recurrence and distant metastases following mastectomy.

High-dose, large volume local-regional irradiation has been shown to be necessary in patients with local-regional recurrence of breast cancer without coexisting distant metastases; however, no studies exist that deal with the dose and volume of local-regional irradiation required for patients with both local-regional recurrence and distant metastases. This report is an analysis of 68 patients who presented with previously untreated local-regional recurrence and coexisting distant metastases. Thirty-five of these patients were treated with local-regional irradiation and systemic therapy; the remaining 33 patients received systemic therapy only. An analysis of the dose and volume in the 35 irradiated patients showed that if the irradiation was inadequate (dose less than 4500 rad and volume not large enough to encompass the entire involved site), the incidence of uncontrolled local-regional disease for the duration of life was 79%, similar to the 64% rate of uncontrolled local-regional disease in the 33 patients not receiving local-regional irradiation. On the other hand, if the dose to the recurrence was at least 4500 rad and if the field was large enough to encompass the entire site containing the recurrence, the incidence of uncontrolled local-regional disease for the duration of life was only 27%. The present study also suggests that local-regional irradiation may be indicated in patients with asymptomatic as well as symptomatic local-regional disease. In patients with distant metastases and initially asymptomatic local-regional disease, adequate irradiation resulted in a lower incidence of ultimate local-regional symptoms when compared to similar patients who were treated with inadequate or no local-regional irradiation. This difference was not quite statistically significant because of the small number of patients in each group.

Radiation therapy alone in the treatment of carcinoma of uterine cervix. I. Analysis of tumor recurrence.

This is a retrospective analysis with emphasis on the patterns of failure in 849 patients with histologically proven invasive carcinoma of the uterine cervix treated with irradiation alone. In 281 patients with Stage IB tumors, the total incidence of pelvic failure was 6.4% (two without and 16 combined with distant metastasis). In 88 patients with Stage IIA, 12.5% failed in the pelvis (one without and ten combined with distant metastasis). The total pelvic failure rate in Stage IIB was 17.4% (22 without and 22 combined with distant metastasis). In 212 patients with Stage III, the overall pelvic failure rate was 35.8% (31 without and 45 combined with distant metastasis). Approximately 25% of the pelvic recurrences were central (cervix or vagina) and 75% parametrial. The overall incidence of distant metastasis was 13.5% for Stage IB, 27.3% for Stage IIA, 23.8% for Stage IIB, and 39.6% in Stage III. Higher doses of irradiation delivered to the medial and lateral parametrium with external beam irradiation and intracavitary insertions were correlated with a lower incidence of parametrial failures in all stages, except IB. In Stage IIA, medial parametrial doses below 9000 rad resulted in 10/78 = 12.8% pelvic failures, in contrast to one recurrence in 10 patients treated with doses over 9000 rad. In Stage IIB, doses below 9000 rad yielded a pelvic recurrence rate of 36/203 (17.7%) compared to 5/49 (10.2%) with higher doses. In Stage III there were 66/167 (39.5%) recurrences with doses below 9000 rad and 10/44 (22.7%) with larger doses. Statistically significant differences were observed among the Stage IIB (P = 0.02) and III patients (P = 0.005) respectively. The lateral parametrial dose also showed some correlation with tumor control, although the differences were not statistically significant. The survival in patients with Stage IIB and III was 10% higher in the patients treated with higher parametrial doses. However, the differences are not statistically significant. These results strongly suggest that higher doses of irradiation must be delivered to patients with Stage IIB and III, but improvement in tumor control must be weighed against an increasing number of complications. Factors other than the total doses of irradiation, such as the characteristics of the tumor and the quality of the intracavitary insertion influence the therapeutic results in irradiation of carcinoma of the uterine cervix. Other therapeutic approaches must be designed to improve the effect of irradiation in the tumor without further injury to the normal tissues. Hypoxic cell sensitizers, hyperthermia and high LET particles are under investigation.

Gestational carcinoma of the female breast.

Few neoplastic diseases can equal the amazing complexity and sheer perversity of carcinoma of the breast. No doubt as many decades of research lie ahead in its study as already have passed. Clinicians have long appreciated the special relationship of the disease to gestation. Diagnosis and treatment of breast cancer during pregnancy represent only a small part of this fascinating relationship. Although indispensable as research tools, animal models pertain to the human disease only in limited, ill-defined ways. The etiology of human breast cancer remains unclear; chemical, viral, hormonal, genetic, and immunologic theories have all been put forward as possibilities. Although gestation clearly alters both the initiation and growth of mammary tumors, its exact role in the various theoretical considerations remains a mystery. The obstetrician-gynecologist holds an important front-line position in the war against breast cancer, as does any provider of primary care to women, and, indeed, as do women themselves. Rather than decrease vigilance during pregnancy, the physician should pursue with extra vigor any breast mass discovered in the gravid patient, when the clinical examination is even less reliable than usual. The finding of a breast mass usually necessitates biopsy. Except for the inclusion of specific pregnancy-related problems, such as galactocele, the diagnostic spectrum of breast masses removed during pregnancy does not differ from that in nonpregnant women. The discovery of a highly suspicious breast mass, or the confirmed biopsy diagnosis of malignancy, in a pregnant patient should indicate the need for referral to a surgical oncologist versed in this unusual problem. The best approach to gestational breast cancer continues to be the team approach, with consultation from specialists in obstetrics, surgical oncology, anesthesiology, nuclear medicine, radiology, radiation oncology, pathology, and medical oncology. The age and general condition of the patient, the extent of the tumor, the stage of gestation, and the informed opinions of the patient and her spouse help to determine the therapeutic strategy. Careful staging not only guides present therapy but also the therapy of future victims through continued investigation. Most surgeons favor operation without delay if cure seems within reach. Mastectomy, with or without cesarean section, can be accomplished without detriment in the hands of a knowledgeable surgeon-anesthesiologist team. By following certain guidelines, the search for metastasis can be conducted safely and appropriately. The clinical situation occasionally may require the initiation of adjuvant radiotherapy or chemotherapy during pregnancy, by experienced consultants. Ongoing studies of tissue hormone receptors and cell kinetics will continue to give insight into the effects of gestational hormones on breast cancer and can aid in the selection of treatment options for the individual patient...

Lung dose in electron beam therapy of chest wall.

The dose to lung tissue in patients whose chest walls are irradiated with 6 and 9 MeV electron beams was estimated. Thermoluminescent dosimetry measurements in thoracic Section 18 of Rando phantom were compared with calculations by two different methods, the effective depth method and the average absorption equivalent thickness (AET) method. The calculations were based on a density of 0.45 (relative to water) for lung tissue in the Rando phantom which was determined from CT scan. The measurements agreed with calculations by the effective depth method within 7 per cent for 9 MeV electron beam at locations where lung tissue thickness was less than 4.5 cm. Larger discrepancy between measurement and calculations was found at greater depths. The effective depth method gave better agreement with measurements (within 14 per cent) compared with the average AET method. The effective depth method was used, to calculate the lung tissue dose at different depths beneath the chest wall. A lung density of 0.25 was assumed to conform to real irradiation situation. The calculations show that for a 9 MeV electron beam dose to lung at 5 cm depth beyond a 2 cm thick chest wall could be as high as 72 per cent of the dose at the maximum buildup depth. It is recommended that post-mastectomy patients with chest wall thickness less than 2 cm should be irradiated with an electron energy of less than 9 MeV or that the chest wall thickness be artificially increased with tissue equivalent bolus.

Prognostic indicators in stage III and localized stage IV breast cancer.

One hundred eighty-three patients with Stage III and nonmetastatic Stage IV breast cancer, seen between 1960-1975 at the Division of Radiation Oncology, Mallinckrodt Institute of Radiology, were retrospectively analyzed to determine the prognostic significance of the following clinical features: (1) "grave signs" (skin ulceration, skin fixation, chest wall fixation, and edema); (2) size of primary tumor; (3) nodal stage; and (4) inflammatory changes. Since therapy among 147 patients with noninflammatory cancer comprised of either irradiation alone (54 patients) or surgery plus irradiation (93 patients), all the above factors were analyzed also with respect to the method of treatment. In 147 patients with noninflammatory carcinoma, the local failure rate, regional failure rate, distant failure rate and five-year disease free survival were all unaffected by the presence or absence of "grave signs," whether treated by irradiation alone or surgery plus irradiation. The size of the primary tumor, in patients treated with irradiation alone, influenced the rate of local failure (44% for tumors 0-8 cm and 76% for tumors greater than or equal to 8 cm) and five-year disease-free survival (30 versus 4%, respectively). Such a statistically significant difference in local failure rate or disease-free survival was not noted when treated with combined modality. N stage also influenced the prognosis in patients treated with irradiation alone since the regional failure rate increased from 9% for N0, N1 to 58% for N2, N3 patients. This was reflected in a decreased disease-free survival (4 versus 30%) for patients with advanced nodal disease who were treated with irradiation alone. No such difference was noted when the nodal disease was treated with a combination of surgery and irradiation. The 36 patients with inflammatory carcinoma had essentially the same incidence of local, regional and distant failure as the 147 patients with noninflammatory carcinoma but the appearance of distant metastases occurred significantly earlier in patients with inflammatory carcinoma than in those with noninflammatory carcinoma. This earlier appearance of distant metastases was reflected in the significantly lower disease-free survival for the patients with inflammatory carcinoma (6 versus 28%). The data from this analysis suggests that consideration should be given to removing the presence of grave signs from the current AJC staging system and substituting in its place the size of the primary tumor (less than 8 cm versus greater than or equal to 8 cm). Further analysis on a large number of patients is needed to substantitate this recommendation.