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The role of particle therapy in the treatment of locally recurrent rectal cancer: a systematic review.

BACKGROUND: Colorectal cancer is a common malignancy. Advancements in multimodality treatment have improved outcomes. About 2-10% of patients will have a local recurrence even after optimal treatment. Salvage surgical treatment is the treatment of choice, however, in posterior and lateral recurrences, surgery is linked to a high rate of treatment-related morbidity. Some recurrences remain unresectable even after neoadjuvant treatment. MATERIALS AND METHODS: A systematic literature review was performed to search for studies on curative-intent radiation therapy (RT) with photons, stereotactic body radiation therapy (SBRT) and particle beam therapy. The aim of the literature search was to define the role of particle therapy in the treatment of patients with unresectable or inoperable local recurrences of rectal cancer where neoadjuvant treatment is unlikely to result in downstaging, leaving patients with RT as the only curative treatment option. RESULTS: 32 studies which fulfil the criteria were identified. In general, SBRT and particle beam therapy permitted the application of significantly higher doses to the target without a concomitant increase in treatment-related toxicities. CONCLUSIONS: For unresectable and inoperable locally recurrent rectal cancer ablative radiotherapy techniques such as SBRT and particle beam therapy offer a curative treatment approach as an alternative to surgery. SBRT can be offered for small local and nodal recurrences, while particle beam therapy can be offered for larger recurrences and complex shapes spanning several anatomical compartments as well. Further research is needed to stratify patients according to their need and eligibility for the different possible modalities of curative-intent RT.

Humans

The value of combined 5-fluorouracil and x-ray therapy in the palliation of locally recurrent and inoperable rectal carcinoma.

The difficulties of treating patients with pelvic recurrence from rectal cancer by further suegery, chemotherapy or by radiotherapy are summarised. Fifty-fibe patients with this form of recurrence are presented to whom 5-fluouracil was administered to improve the effectiveness of radiotherapy. A safe and effective regime is described which produced complete relief of pain in 66 percent of the patients who presented with this symptom with a further 16 percent obtaining partial relief. Total resolution of tumour masses and complete relief from mucoid rectal discharge were achieved less often, although the majority of patients derived benefit from treatment. An important finding of this study has been that in this particular group of patients a short, low-dose course of combined therapy was as effective, both in the relief of symptoms and the prolongation of survival, as more prolonged high-dose treatment.

Fluorouracil

Role of simple mastectomy in treating patients with breast cancer.

From 1945 to 1971, 473 patients had simple mastectomies as the primary treatment for their breast cancer (421 had either a simple mastectomy alone [26%], a simple mastectomy followed by postoperative radiation therapy [64%], or preoperative irradiation followed by simple mastectomy [10%]). More than one half of these patients were "inoperable" by standard surgical criteria. The local recurrence rate was 24%, which compares favorably with the reported 48% local recurrence rate for "inoperable" patients treated by radical mastectomy. These recurrences were on the chest wall in two thirds of the patients and in the regional lymph nodes of the other third. No statistical differences in survival or recurrence rate could be correlated with the site of the primary cancers in the breasts or among the three treatment groups.

Breast Neoplasms

Adenoid cystic carcinoma (cylindroma) in the head and neck. A clinical review of 82 cases.

A review of 82 cases of adenoid cystic carcinoma in the head and neck is given. Radical surgery was carried out in 33 patients and yielded the best long-term results. Radiation therapy was given to 43 patients for inoperable tumour, local recurrence or, postoperatively, for sub-clinical disease. It proved especially valuable in obtaining remissions from local recurrence.

Adolescent

Intraarterial infusion chemotherapy (5-fluorouracil) in patients with inextirpable or locally recurrent rectal cancer.

A retrospective analysis of the results of treatment of advanced rectal cancer of the pelvis with regional intraarterial infusion of 5-fluorouracil (5-FU) is reported. A special technic for positioning the catheters selectively in the internal iliac arteries justifies this analysis. Four patients with primary inextirpable rectal cancer and 10 patients with locally recurrent rectal cancer have been treated. No immediate mortality was noted. Relief of pain was noted in two-thirds of the patients. An objective tumor response was noted in three patients with locally recurrent disease. In one patient with primary inoperable cancer it was possible to extirpate the tumor after infusion therapy. An improvement in quality of life during the first 2 months after therapy was achieved in half of the patients as judged by their performance. Complications were not serious. Hematomas with infection were seen in one patient, two patients had septicemia, and three patients had transient oliguria. Transient thrombocytopenia was reported in two patients. The results indicate that infusion therapy produces a reasonable response such as palliation of pain. Only minor complications were seen and easily controlled. The advantages of infusion therapy are that it can be given in a reasonable time with only a short hospital stay.

Adult

Combined cranio-orbital surgery for extensive malignant neoplasms of the orbit.

Extensive, invasive neoplasms of the cranio-orbital region are generally considered to be inoperable and are treated with local radiation therapy and occasionally with chemotherapy. Upon local recurrence of these neoplasms, further treatment efforts are usually deemed futile. Over the past 4 years, 10 patients with extensive neoplasms of the cranio-orbital region that were previously thought to be inoperable were referred to us for further evaluation. Five of these patients had failed an intensive course of radiation therapy. Radical regional cranio-orbital resection was performed. The resection included the skin, globe, sphenoid wings, and orbitofrontal bone. The maxillary sinus and nasal septum were left exposed. The exposed dura mater and the frontal and temporal bones were resurfaced with split-thickness skin grafts. All patients in this series have survived free of local disease to date. Combined cranio-orbital resection offers both palliation and a possible cure for patients with extensive, invasive neoplasms of the cranio-orbital region. Reconstructive surgery can be performed using full-thickness flaps after 2 years of observation for local recurrence.

Adolescent

[Bladder carcinoma: therapeutic concept of the Urology Department of the University Hospital, Mainz].

A therapeutic concept based on tumor staging and grading is presented: T0N0M0 - urine cytology positive - cystoscopy every 3 months. Transitional cell carcinoma (90%): T(iS)N0M0 - carcinoma in situ - cystoscopic biopsy every 3 months. Cystectomy with commencing tumor infiltration. T1N0M0 (80% of all bladder tumors): T1N0M0G0 - TUR; cystoscopy every 3 months. T1N0M0G1-3 - TUR; control-TUR 6 weeks later with systematic biopsy. G3 with tumor recurrence - cystectomy. T2N0/N1M0; G1-2 - TUR; local chemotherapy (adriamycin). G3 - cystectomy; high voltage treatment in inoperable patients. T4NxMx - symptomatic-palliative therapy: TUR, urinary diversion. Squamous cell carcinoma (2-5%): as transitional cell carcinoma; with high voltage therapy adjuvant chemotherapy using bleomycine. Adenocarcinoma (2-3%): as transitional cell carcinoma; cystectomy including part of the anterior abdominal wall and umbilicus. Immunostaging (assessment of the immunocompetence) should be part of the diagnostic procedures and follow-up examination.

Adenocarcinoma

Liver tumors in children in the particular reference to hepatoblastoma and hepatocellular carcinoma: American Academy of Pediatrics Surgical Section Survey--1974.

A review of 227 cases of hepatoblastoma, hepatic cell carcinoma in children seen in the United States over a 10-yr period is presented. Both tumors were seen most commonly in infancy, but the hepatocellular carcinoma shows a second peak of incidence around puberty. Males predominated in both diseases more so in hepatoblastoma. Presenting symptoms in both diseases were very similar, most commonly an upper abdominal mass or abdominal enlargement associated with anorexia and weight loss. In the preoperative evaluation the presence of alpha-feto protein was one of the most helpful diagnostic tests. Disturbances of liver function were usually mild but were more marked in those children with hepatocellular carcinoma. Preoperative x-rays were abnormal in a large percentage of cases with the hepatic arteriogram and vena cavagram being the most useful diagnostic x-rays for liver tumors. Liver scans were positive for liver tumor in 95% of the children when this test was carried out. The follow-up for these patients ranged from 2 to 10 yr. The size of the primary tumor did not appear to correlate with survival but bilateral location of the tumor, 33% in hepatoblastoma and 45% in hepatocellular carcinoma, made many of these tumors inoperable. Multicentric tumors were also found in a large number of patients, being more common in hepatocellular carcinoma. There was a high rate of local recurrence or local extension after operation in both diseases, and metastatic spread was similar being most common to the lungs and abdomen. A wide variety of surgical procedures were carried out in these patients from biopsy only to extended hepatic lobectomy. When incomplete excision or biopsy only was carried out no patient survived in either group. Among the hepatoblastoma patients, 45 of 78 patients who had complete excision are surviving. In the hepatocellular carcinoma patients where the operability rate was much lower 12 of 33 patients are surviving when tumor was completely excised. Complications were frequent, the most common being excessive blood loss at operation. There were eight operative deaths and 17 postoperative deaths in the combined group. There was no evidence that radiation therapy or chemotherapy controlled disease which could not be completely excised surgically. The only direct evidence of a favorable effect of radiation and chemotherapy were three cases of hepatoblastoma in which the tumor changed from inoperable to operable by a combination of radiation therapy and multiple drug chemotherapy. Both tumors are highly malignant, and 90% of the children who died of hepatoblastoma died within 12 mo of diagnosis. In the hepatocellular carcinoma 80% of the deaths occurred within 1 yr of diagnosis. At this time it seems that operative excision offers the only chance of cure in children with these tumors and cure rates of 60% can be expected with hepatoblastoma and 33% in hepatocellular carcinoma if the tumor can be completely excised.

Adolescent

[Radiotherapy of colorectal carcinomas (author's transl)].

The authors are of the opinion that radiotherapy is always indicated for colorectal carcinoma patients: (1) Operable carcinomas should be given radiation treatment before operation; postoperative saturation of high-risk cases at the full tumor dose is recommended. (2) Inoperable or partially operated carcinomas should be treated with tumoricidal radiation dose. (3) Radiotherapy is also indicated for cases of local recurrence, especially in the floor of the pelvis, in view of the frequent lack of possible operative access. The necessary dose rate must take into account any prior radiation load. (4) The excellent palliative results are themselves a recommendation for radiotherapy.

Aftercare

Radiation therapy in the treatment of malignant salivary gland tumors.

A retrospective analysis of 52 patients with malignant salivary gland tumors is reported. Seventeen patients received early postoperative radiation therapy and 16 (94%) were free of local or regional disease 2-14 years following initiation of therapy, although 14 were considered at high risk of developing local recurrence. Two subjects (12%) developed distant metastases and 14 (82%) were completely disease-free. Survival and disease-free status of patients treated for recurrent or inoperable disease were much worse with two of 13 disease-free at 45 and 168 months respectively. Various workers have reported recurrence rates after surgery along at 25-38% and over 50% for many histological types. On the basis of this report early postoperative radiation therapy is recommended to reduce the risk of postsurgical recurrence. Prognostic trends relating to both histological type and location of primary disease are discussed.

Adenocarcinoma

Preoperative irradiation of cancer of the lung: final report of a therapeutic trial. A collaborative study.

Between May, 1963 and December, 1966, 17 medical centers cooperated in two separate but integrated therapeutic trials of primary lung cancer. One study was of patients with lesions considered operable at the time of diagnosis, and the other of patients with initially inoperable cancer but who were considered potentially operable after radiotherapy. Patients operable at the time of diagnosis were randomly assigned to receive either immediate surgery (278 patients) or preoperative radiotherapy followed by surgery (290 patients). All but one were followed until death or 5 years survival. Survival to each anniversary after randomization was almost identical for the two groups. At 5 years the survival rate was 14% after preoperative radiotherapy and 16% after immediate surgery. On the basis of the small standard error of the difference between these survival rates, a large advantage or a large disadvantage for preoperative radiotherapy is unlikely. Recurrence of cancer either locally or as distant metastasis was also similar in the two groups. Postoperative mortality was estimated to be 11% in the immediate surgery group, but cannot be estimated in a comparable fashion for the irradiated group. Certain postoperative complications were more frequent in the irradiated group, but survival during the first was not affected. Out of 425 patients initially considered to be inoperable, 152 were considered resectable after radiotherapy. These patients were randomly assigned to have either a thoracotomy and resection of their cancer if possible (78 patients) or no surgery (74 patients). Survival to each anniversary after randomization was very similar. After 5 years the survival rate was 8% for the group assigned to surgery and 6% for the group assigned to no surgery. The difference has a standard error of 4%.

Carcinoma, Small Cell

[Intrastitial iodine-131 administration in inoperable thyroid gland cancer].

The authors report the indications to and the results of clinical application of interstitial injections of iodine-131 in unresectable tumors, recurrences and regional metastases of thyroid cancer. Interstitial injection of iodine-131 in 35 inoperable patients (66 injections of iodine-131) made it possible to reduce considerably the size of tumor by 1 g of the tumor, on the average, were of the order of 5140 rad, radiation exposure of blood and kidneys--0.03 rad/litre and 139 rad, accordingly. Neither complications nor grave local and general reactions were noted.

Adenocarcinoma

[Radiation therapy of anal carcinome. Experiences in 28 cases during the years 1950 to 1975 (author's transl)].

From 1950 to 1975, there were 28 patients with anal cancer irradiated in the University Clinic for Nuclear Medicine of the Kantonsspital Zürich. All patients with small and perianally situated tumors were cured by radiotherapy. In advanced lesions, the cure rate was about 10 to 20%. Our own results and a review of the literature shows, that in most cases of anal cancer surgical treatment should be preferred. Radiotherapy should be reserved for small and superficial perianal lesions and for inoperable lesions. Treatment results may be improved by a combined treatment with surgery and irradiation.

Adult

[The place of radiation therapy in the treatment of giant cell tumors of bone (osteoclastomas): results from 32 cases (author's transl)].

Radiotherapeutic results of giant-cell tumors of the bone in 32 own cases are presented. The frequency of local recurrency was 30%, the 10-year survival rate was somewhat about 70% and in nearly 12% of primary benign giant-cell tumors there appeared malignant transformations (inclusive two fibrosarcomas in irradiated tissue). In other radiotherapeutic series, the frequency of malignant transformation is between 14 and 19%, in series with primary surgical therapy the rate of secundary malignant transformation is between 3 and 10%. Despite of the limited comparability of the surgical and radiotherapeutic material, we recommend in accordance with most authors in operable lesions surgical treatment. In inoperable lesions or when the lesion is not radically operable, radiation therapy has a definite place in the treatment of giant-cell tumors of the bone with a curative rate of about 80%.

Adolescent

[Problems in radiation therapy for carcinoma of the rectum (author's transl)].

The role of radiation therapy within the total treatment for carcinoma of the rectum is reported in this paper. Early treatment with radiological contact methods as well as systemic post operative irradiation of advanced tumor stages are interpreted in detail, and attention is drawn to the importance of pre-operative irradiation meanwhile being tested at many places. Therapy of recurrences and of inoperable tumor stages, including chemotherapy, is explained on the basis of own experiences and of reviewing the data of the literature.

Humans