Carcinoma of the female urethra: a review of results with radiation therapy

Low stage female urethral carcinoma is curable by radiation therapy alone and is amenable to brachytherapy techniques whereby high doses of irradiation can be delivered safely. A 60 to 80 per cent 5-year survival rate with preservation of bladder function and control can be expected with good radiotherapeutic techniques. Except for stage Tis or early stage T1 lesions of the anterior urethra that can be treated with limited surgical excision, irradiation should be considered as an alternative to more extensive surgery for low stage bulky lesions. While there has been some success with radiation therapy alone for advanced disease, the cure rate probably can be improved with a combined approach using surgery, radiation therapy and possibly chemotherapy.     

Actinomycin-D therapy in testicular cancer (author's transl)]

In early stages of the disease the prognosis of testicular cancer has been improved mainly by the introduction of radical surgical procedures. Cytostatic treatment of metastasising testicular cancers has only been of limited value. Actinomycin D has been shown to be one of the most potent agents in malignant teratomas. Own results are presented for 21 eligible patients who received actinomycin D alone. One complete remission and 4-partial remissions were achieved giving an overall response rate of 19%. This precentage seems to be low compared to similar data in the current literature. The result may be explained by the selection of the patients with a high percentage showing far advanced disease before therapy was initiated. However, comparing the data presented with those from our own study on combination chemotherapy and with the more recent results in the literature, single agent chemotherapy does not seem to be the method of choice in metastasising testicular cancer. Improvement of the results by the integration of combination chemotherapy, hormonal therapy and irradiation will have to be based on prospective, controlled studies.     

Combined therapy for inflammatory breast cancer

The prognosis for patients with inflammatory breast cancer has improved in recent years. This review was undertaken to evaluate current management in three Milwaukee (Wis) hospitals and to identify determinants of prognosis. We identified 25 patients with inflammatory breast carcinoma diagnosed between 1967 and 1987. Most of the patients were treated with combination chemotherapy and radiation therapy, and 10 had mastectomies. The 5-year survival of patients without initial distant metastases was 24%. The 5-year survival of patients who received chemotherapy before local treatment was 40%. Patients who had clinically involved axillary nodes or a palpable mass in the breast had poorer survival than those who did not; the presence of dermal lymphatic invasion had no significant effect on survival. Initial chemotherapy has become an important part of the care of patients with inflammatory breast cancer. It remains uncertain whether mastectomy improves on irradiation in achieving local control or improves survival.     

Treatment of stages B3 and C seminoma with chemotherapy followed by irradiation therapy. Southwest Oncology Group Study.

Beginning in 1981, 28 patients with advanced seminoma were treated with combination chemotherapy followed by irradiation to evaluate the possibility of improved survival using both modalities. The treatment protocol consisted of two courses of vincristine, actinomycin-D, and cyclophosphamide followed by reassessment. Those initially presenting with Stage B3 disease who achieved a complete response to two cycles of chemotherapy then underwent irradiation. All others were given a third course of chemotherapy before undergoing irradiation. The pre-radiation portion of this protocol produced a complete response rate of only 25 percent, substantially less than other, more recent, protocols. Radiation therapy produced a complete response in 69 percent of those who did not achieve a complete response from chemotherapy, increasing the complete response rate from 25 percent to 64 percent. Given this response rate to radiation therapy and the difficulty of dissection and associated morbidity with the surgical excision of postchemotherapy residual masses, the best option at this time may be observation with salvage chemotherapy and/or radiation reserved for those with disease progression.     

Surgical resection of limited disease small cell lung cancer in the new era of platinum chemotherapy: Its time has come

OBJECTIVE: Although resection is not the standard of care in treating small cell lung cancer, new platinum drugs and modern staging have allowed the role of surgery to be reevaluated. METHODS: We reviewed our institutional experience of 1415 patients with small cell lung cancer from 1976 to 2002 among whom 82 (6%) underwent surgery with curative intent. RESULTS: Median age at surgery was 62 years, and small cell lung cancer of mixed morphology represented 14 of 82 (17%). Treatment consisted of surgery alone in 11% of cases (9/82), surgery with neoadjuvant therapy in 22% (18/82), and surgery with adjuvant therapy in 55% (45/82). Prophylactic cranial irradiation was given to 23% (19/82). The 5-year survival of the entire cohort was 42%. The 5-year survival of patients receiving adjuvant chemotherapy (n = 41) was significantly different according to whether patients had received platinum or nonplatinum regimens (68% vs 32.2%, P = .04). Among patients with stage I disease who received adjuvant chemotherapy (n = 24), the 5-year survivals for patients receiving platinum and nonplatinum chemotherapy were 86% and 42%, respectively ( P < .02). If patients who received either neoadjuvant or adjuvant therapy (n = 56) were considered, the 5-year survival was significantly better for platinum than for nonplatinum chemotherapy (62% vs 36%, P = .05). The 5-year survival was also better for those undergoing lobectomies (n = 52) than for those with limited resections (n = 15, 50% vs 20%, P = .03). Survival outcomes also differed by gender, with female patients having a 5-year survival advantage over male patients (60% vs 28%, P = .004). CONCLUSION: These results support a reevaluation of the role of surgery in the multimodality therapy for small cell lung cancer, which currently includes only radiotherapy and chemotherapy.     

Natural history of surgically treated mucosal melanoma

Thirty-three patients with melanoma arising in a mucosal site were reviewed. Sixteen patients were treated either with abdominoperineal resection or radical vulvectomy and superficial inguinal lymphadenectomy. Three patients were treated palliatively. Fourteen patients were treated conservatively with local excision, wide local excision, and radiation therapy. One patient received systemic chemotherapy and radiation therapy. Local recurrence developed in seven patients. The overall survival rate was poor. Neither local control nor survival appeared to be influenced by the initial surgical approach.     

Toxicity of photodynamic therapy after combined external beam radiotherapy and intraluminal brachytherapy for carcinoma of the upper aerodigestive tract

BACKGROUND AND OBJECTIVE: To describe the toxicity of photodynamic therapy (PDT) in patients with carcinoma of the upper aerodigestive tract who received prior treatment with external beam irradiation and intraluminal brachytherapy (IB). STUDY DESIGN/MATERIALS AND METHODS: Hospital records of PDT patients were reviewed. Three patients who received prior treatment with external beam irradiation and IB were identified. Two patients had esophageal carcinoma treated with combined chemotherapy and external beam irradiation (55.8 and 50.4 Gy) followed by IB (12 Gy and 35 Gy at 1 cm). These patients then received PDT for treatment of recurrence (2 mg/kg Photofrin injection and 2 light applications: 630 nm, 150--200 J/cm, 200--400 mW/cm). One patient had non-small cell lung cancer treated with external beam irradiation (60 Gy) followed by IB (36.1 Gy at 1 cm) and then received PDT for recurrence (1 mg/kg Photofrin injection and one light application: 630 nm, 150 J/cm, 200 mW/cm). RESULTS: One patient with esophagus cancer had formation of a tracheoesophageal fistula, which required stent placement. The other esophageal cancer patient developed quadriplegia due to an epidural abscess arising from a fistula with the diseased portion of the esophagus. The lung cancer patient had massive hemoptysis after the procedure and died 2 days later. Autopsy showed necrotizing arteritis of the right pulmonary artery. CONCLUSION: Patients with upper aerodigestive tract carcinoma who have received treatment with both external beam irradiation and IB seem to be at higher risk for complications when treated with PDT.     

Carcinoma of the breast in women 80 years of age and older: still a lethal disease

Cancer of the breast is a frequent and potentially lethal problem in women 80 years of age and older. In our experience, many present with advanced disease which indicates the continuing need for patient and doctor education concerning the significance of a breast lump in the elderly. Although many of these patients have other diseases, only a small number, if thoughtfully managed, will not be fit for appropriate standard methods of treatment. In the majority of patients who died, death was due to the breast cancer and many who did die from other causes had the added misery of persisting or metastatic breast cancer. In those patients with potentially curable cancer, we recommend either wide local excision, axillary node dissection and irradiation, or modified radical mastectomy. When simple mastectomy alone is used, there is a very high local recurrence rate. Although the patients studied were treated before the era of tamoxifen therapy, it is noteworthy that hormone manipulation would be of value in many of these patients and in selected cases, chemotherapy should also be considered.     

Surgical management of advanced or recurrent endometrial cancer

Most patients who have endometrial cancer are diagnosed with early stage disease and have excellent long-term survival. For patients who have evidence of metastatic disease at surgery, there is a survival benefit to be gained if all gross evidence of disease can be resected. Even in cases in which complete gross excision cannot be attained, surgical debulking to small-volume residual disease leads to an improved prognosis compared with patients left with bulky residual disease. Patients with endometrial cancer who have not previously received pelvic irradiation and develop isolated pelvic recurrences can be effectively treated with pelvic radiotherapy. The treatment options for patients who develop recurrent disease are limited. Hormonal and chemotherapeutic treatments typically do not provide durable responses. In carefully selected patients with isolated central recurrences, pelvic exenteration is the only potential option for cure. Long-term survival has been achieved although complication rates are significant. Further investigation into the techniques of IORT may increase the pool of patients for whom surgically based salvage therapy may be offered.     

Histological effects of hormono-chemotherapy on prostatic cancer]

Using new criteria for histological effects of anti-cancer treatment, the effects of hormono-chemotherapy on 10 patients with prostatic cancer not previously treated were compared with those on 10 patients who received conventional hormone therapy. Marked effects were observed in 4 (40%) patients received hormono-chemotherapy but not observed in patients who received conventional hormone therapy (chi 2 test, p less than 0.05). All four cases who showed marked effects were in stage B at the beginning of treatment. Hormonal effects were more obvious in well differentiated cancer, and the effects of chemotherapy were observed in some cases with moderately and poorly differentiated cancer. Therefore, the addition of chemotherapy is recommended as the initial therapy on prostatic cancer to reduce the relapsing rate, especially for patients with poorly and moderately differentiated cancer.     

Long-term follow-up of the first breast conservation trial: Guy' wide excision study

Breast conservation therapy is now accepted as a proven approach for selected patients with operable breast cancer. Nevertheless, it is important to appreciate that the first randomized trials, which were carried out at Guy's Hospital, indicated the need for good local control and the increased mortality from breast cancer which occurred when treatment was sub-optimal. In the first trial 374 women aged > or = 50, with T1, T2, N0 and N1 tumours were randomized to either Halsted mastectomy and postoperative radiotherapy or wide excision and postoperative irradiation. Both groups were given 25-27 Gy to the gland fields and the wide excision group received additionally 35-38 Gy to the breast. Hence the wide excision group had no axillary surgery and subsequent axillary irradiation using what is now regarded as a low dose of radiotherapy. After 25 years, local relapse has occurred in 26% of the mastectomy group and 50% of the wide excision group (chi(2)= 21.6, P < 0.001). The breast cancer mortality rate at 25 years was 56% in the mastectomy group and 63% in those treated by wide excision (chi(2)= 5.33, P= 0.02). The first analysis of this trial indicated that increased risk of axillary relapse was restricted to N1 cases and so a second trial was conducted with entry only for those with clinically negative axillae (N0 series). Of 255 cases entered, 133 were randomized to mastectomy and 122 to wide excision. The same radiotherapy schedule was used as in the original Series. After 25 years local relapse occurred in 18% of the mastectomy cases and 54% of the wide excision group (chi(2)= 30.6, P < 0.001). There were significantly more distant relapse in the latter group (chi(2)= 6.32, P= 0.01), and a significant increase in breast cancer deaths (57% versus 44%, chi(2)= 4.27, P= 0.04). These two trials, conducted before the widespread introduction of systemic adjuvant therapy, both indicate the long-term effects of inadequate primary treatment. Inadvertent failure to treat the axilla effectively led not only to significantly increased axillary relapse rates but also to more deaths from metastatic disease.     

Targeted infusions of supradose Cisplatin with systemic neutralization for carcinomas invading the temporal bone

In an attempt to improve the dismal prognosis for patients with advanced cancer involving the temporal bone, a regional chemotherapy technique was piloted as part of the multimodality therapy for such patients. Rapid supradose cisplatin infusions selectively delivered to the lesion were given to 14 patients with carcinoma involving the temporal bone. Concurrent systemic cisplatin neutralization was achieved with sodium thiosulfate which permitted the use of cisplatin dose intensity regimens equivalent to fivefold the conventional amount. Four patients received chemotherapy alone, four had concomitant irradiation, and six had subsequent irradiation and/or temporal bone surgery. All patients tolerated the chemotherapy without significant complications or toxicity.All three of the patients with previously untreated disease responded to chemotherapy (2 Crs, 1 PR); three of the seven patients with recurrent disease responded to chemotherapy; and all four patients treated with chemoradiation had a complete response (including one patient with recurrent disease). The median follow-up time was 19 months (range, 5 to 63 months). Nine of the 14 patients are alive, including the 4 who were treated with targeted chemoradiation.The use of targeted high-dose chemotherapy for patients with malignant skull base lesions offers hope for improved outcome, particularly when this regimen is given simultaneously with radiation.     

Possible radiation induced cancer of the thoracic esophagus after postoperative irradiation in breast cancer

We report 11 cases with cancer of the thoracic esophagus developing after postoperative irradiation therapy for the breast cancer. Irradiation was done immediately after mastectomy in these cases and the irradiation field included the unilateral or bilateral parasternal region. They received a total dose ranging from 35 Gy to 60 Gy and the dose received to the thoracic esophagus was estimated from 10 Gy to 48 Gy. All cancer sites were involved in the irradiation filed. The latent intervals of 10 cases from radiation to the manifest of cancer ranged between 10 to 19 years. Among 4777 women undergone mastectomy for breast cancer between 1946 and 1980 in our hospital, 8 women (0.17%) developed cancer of the thoracic esophagus, whereas 5 (0.335%) out of 1534 women treated with mastectomy and radiotherapy with Linac between 1964 and 1980 developed cancer of the thoracic esophagus. Higher incidence of esophageal cancer in patients treated with surgery and radiation suggests that these cancers might be induced by radiation. Eight patients had esophagectomy and 4 patients of them received postoperative irradiation. They have survived from 9 months to 13 years. Two patients were controlled well by the irradiation alone. It is interesting that radiation therapy is sensitive to the possible radiation induced cancer of the thoracic esophagus. Follow up study should be directed to the possible development of second malignancy in patients who survive for a long time after radiation therapy.     

Management of carcinoma of the rectum and anus without abdominoperineal resection

Since 1979, 16 patients with cancer of the rectum and anus have been treated without abdominoperineal resection. All have received radiotherapy. Nine of these had local excision before receiving radiotherapy. There has been no evidence of recurrent cancer in 15 of the 16 patients with a median follow-up period of 24 months (range 14 to 52 months) for a recurrence rate of 6 percent. We conclude that limited excision, radiotherapy, or both are viable alternatives to abdominoperineal resection of small, early cancers of the rectum and anus.     

Effect of intravenous hyperalimentation on established delayed hypersensitivity in the cancer patient.

Forty-seven cancer patients were selected for study based on their candidacy for hyperalimentation. Each patient received selected skin test antigens intradermally in the forearm prior to the initiation of hyperalimentation, and at 7-day intervals throughout treatment with either chemotherapy, radiation therapy or surgery. Of 23 patients who received chemotherapy, 17 initially had negative skin tests. Thirteen of these patients had positive skin tests after an average of 11.4 +/- 5.5 days of hyperalimentation. Response to chemotherapy occurred only in hyperalimentation. Response to chemotherapy occurred only in those patients whose skin tests were positive, and conversion of skin test reactivity to positive occurred before clinical regression of metastatic disease. No patient who received radiation therapy developed or retained positive skin test reactivity, although nutritional repletion was considered satisfactory in each patient. Surgical patients whose skin tests converted to positive or remained positive preoperatively had an uncomplicated postoperative recovery, whereas 2 of 4 patients whose skin tests remained negative expired postoperatively. Absence of established delayed hypersensitivity in the cancer patient who is treated with chemotherapy or surgery is probably secondary to generalized malnutrition, and established cell-mediated immunity can be restored by proper nutritional repletion.     

Recurrent squamous cell carcinoma of the anal canal. Predictors of initial treatment failure and results of salvage therapy.

OBJECTIVE: The outcomes of patients with squamous cell carcinoma of the anal canal treated by either sphincter-preserving procedures or radical surgery were evaluated, with the goals of identifying factors predicting treatment failure and quantifying results of salvage therapy in patients with recurrent disease. BASIC PROCEDURES: A population-based study on all patients in all 159 hospitals of the Department of Veterans Affairs (VA) from 1987 to 1991 was carried out. Data were compiled from several national computerized VA data sets. Supplementary information from local tumor registrars also was obtained, including demographic information, discharge summaries, operative reports, pathology reports, and medical oncology and radiation oncology summaries. From these sources, information on tumor histology, tumor stage, tumor grade, presence of regional or distant metastases, surgical procedures, use of chemotherapy and radiation therapy (RT), toxicity of chemotherapy and RT, development of recurrent disease, treatment of recurrence, survival, and cause of death were obtained. MAIN FINDINGS: Four hundred five patients with anal cancer were identified by computer search, and 204 (51%) were evaluable; 164 of 204 (80%) had squamous cell carcinoma, 137 of whom (84%) were treated with sphincter-preserving procedures, and 27 of whom (16%) were treated by by radical surgery. One hundred fourteen of 138 (83%) were treated by multimodality therapy, which we defined as local excision followed by chemotherapy and RT. The mean dose of RT among patients treated by multimodality therapy was 4200 +/- 540 cGy and 82% of those treated with multimodality therapy received 5-FU/mitomycin C. Recurrent disease was diagnosed in 43 of all 149 patients (29%) with potentially curable disease. (stages I-III) Multivariate analysis revealed that stage at diagnosis (p = 0.04) and method of treatment (p = 0.03) were the sole predictors of recurrence. Fifty-three percent of patients who underwent salvage abdominoperineal resection (APR) are alive, whereas only 19% who underwent salvage chemotherapy with or without RT are alive. PRINCIPAL CONCLUSIONS: These data indicate that multimodality therapy currently is being employed in the majority of patients with squamous cell carcinoma of the anal canal in the VA system. Tumor stage and method of treatment appear to affect the likelihood of development of recurrent disease. Salvage APR has curative potential. Results with salvage chemotherapy and RT are disappointing.     

Efficacy of routine follow-up after first-line treatment for testicular cancer

To define guidelines for the follow-up management of patients treated for testicular germ cell tumor this study assessed characteristics of patients with recurrent disease. The charts of 505 patients with testicular cancer treated and followed-up at the University Medical Centre Nijmegen between 1982–2000 were reviewed retrospectively. In 42 patients disease recurrence was found during routine follow-up. In a subset of patients no recurrences were seen after first-line treatment: (a) pathological stage IIa nonseminoma patients who were adjuvantly treated with chemotherapy and (b) histologically confirmed complete responders after primary chemotherapy. Furthermore, in low-stage disease no intra-abdominal recurrences were seen in (a) pathological stage I nonseminoma patients and (b) low-stage seminoma patients who received radiotherapy. The risk of recurrent testicular cancer depends on primary therapy and efficacy of it; these results indicate a limited role for follow-up in pathological stage II nonseminoma patients adjuvantly treated with chemotherapy and in histologically confirmed complete responders after chemotherapy. Abdominal computed tomography does not appear necessary in routine follow-up of patients treated for low-stage testicular cancer.     

Neoadjuvant therapy and bladder substitute for invasive bladder cancer: 20 years experience at Tohoku University

BACKGROUND: Neobladder, using the intestine, was performed after neoadjuvant therapy and total cystectomy as a treatment for invasive bladder cancer. METHODS: Between January 1977 and April 1997, an ileocecal neobladder was used for 23 patients and a sigmoid neobladder was chosen for use in 32 patients. For the diagnosis of invasive bladder cancer and the evaluation of neoadjuvant therapy, we used whole-layer core biopsy (WLCB) of the bladder tumor and fine needle aspiration biopsy (FNAB) of pelvic lymph nodes after bipedal lymphography. For neoadjuvant therapy, two to four courses of internal iliac arterial infusion chemotherapy (IIA) were undertaken in 32 patients. Five patients were treated with IIA combined with 40 Gy irradiation to the pelvic space. RESULTS: Pretreatment WLCB revealed a tumor of stage T2b or greater in 10 patients. After neoadjuvant therapy, three patients were down-staged to pT0. In five patients, pretreatment FNAB revealed pelvic lymph node metastases that were not detected by computed tomography or magnetic resonance imaging. Fine needle aspiration biopsy post-neoadjuvant therapy revealed tumor stage N0 in all patients and lymph node dissection revealed pN0 in four patients. Of the five patients who received 40 Gy irradiation, none had any postoperative complications, such as intestinal fistula or urinary leakage. Four male patients (10%) had urethral recurrence, but all were successfully treated by transurethral resection. Two patients treated prior to 1985 experienced local recurrence. Neither was treated by neoadjuvant therapy. Eight patients who died after 1985 had metastatic cancer, but none had local recurrence. None of the patients who received a sigmoid neobladder required clean intermittent catheterization or had bilateral vesico-ureteral reflux. CONCLUSIONS: Neoadjuvant therapy seems to reduce local recurrence in invasive bladder cancer. The sigmoid colon may be suitable for neobladder.     

Targeted Infusions of Supradose Cisplatin With Systemic Neutralization for Carcinomas Invading the Temporal Bone

In an attempt to improve the dismal prognosis for patients with advanced cancer involving the temporal bone, a regional chemotherapy technique was piloted as part of the multimodality therapy for such patients. Rapid supradose cisplatin infusions selectively delivered to the lesion were given to 14 patients with carcinoma involving the temporal bone. Concurrent systemic cisplatin neutralization was achieved with sodium thiosulfate which permitted the use of cisplatin dose intensity regimens equivalent to fivefold the conventional amount. Four patients received chemotherapy alone, four had concomitant irradiation, and six had subsequent irradiation and/or temporal bone surgery. All patients tolerated the chemotherapy without significant complications or toxicity.

All three of the patients with previously untreated disease responded to chemotherapy (2 Crs, 1 PR); three of the seven patients with recurrent disease responded to chemotherapy; and all four patients treated with chemoradiation had a complete response (including one patient with recurrent disease). The median follow-up time was 19 months (range, 5 to 63 months). Nine of the 14 patients are alive, including the 4 who were treated with targeted chemoradiation.

The use of targeted high-dose chemotherapy for patients with malignant skull base lesions offers hope for improved outcome, particularly when this regimen is given simultaneously with radiation.

     

Survival results from a phase III study of simultaneous versus 1-hour sequential methotrexate-5-fluorouracil chemotherapy in head and neck cancer

There were 79 patients with squamous cell head and neck cancer randomized to receive simultaneous or 1 hour sequential methotrexate-5 fluorouracil (MTX--5-FU) chemotherapy: 47 patients were previously untreated and 32 patients had recurrent disease. The treatment groups were comparable for important prognostic features. The median survival for the 47 newly presenting patients was 22 months and for recurrent disease patients was 14 months. No difference could be detected in the survival of patients who received simultaneous versus sequential chemotherapy. When only chemotherapy responders were compared, no difference in survival was detected for those who received sequential versus simultaneous therapy. Subsequently, 19 chemotherapy responders received radical radiation therapy, and 15 were rendered disease-free whereas only 4 of 17 chemotherapy nonresponders were rendered disease-free by subsequent radiation (P = .002). The survival of the 19 chemotherapy responders was 34 months compared with 16 months for the 17 chemotherapy nonresponders treated with radiation. We conclude that there is no therapeutic advantage for 1 hour sequential MTX-5 FU chemotherapy compared with simultaneous use of these drugs in squamous cell head and neck cancer. Chemotherapy responders are more likely to respond to radiation therapy.