Osteosarcoma: A Multifactorial Clinical and Histopathological Study with Special Regard to Therapy and Survival

A multifactorial analysis was performed on all 153 unequivocal cases of genuine osteosarcoma recorded in the Swedish Cancer Registry for the years 1958 through 1968. Cases of so-called parosteal osteosarcoma, soft-tissue osteosarcoma and osteosarcoma secondary to Paget's disease of bone were not included. The osteosarcomas were subclassifiecl as follows: osteoblastic (69 per cent), chondroblastic (19 per cent) and fibroblastic (12 per cent). The overall 5-year survival rate was 22 per cent; 55 per cent for those who had undergone amputation above the joint proximal to the involved skeletal part, 22 per cent for those amputated on the involved skeletal part, 11 per cent for those treated with local extirpation of the tumor, and 1 per cent in cases in which the lesion was not radically removed. Tumors of the femur, humerus and scapula were as malignant as axial tumors. The former carried a 5-year survival rate of 13 per cent, regardless of whether the patients had been treated with exarticulation or amputation on the involved skeletal part. Patients with axial tumors showed a 5-year survival rate of 15 per cent. These survival data suggest that proximal amputation alone might suffice for lesions situated distally to the knee and elbow joints, while tumors in the humerus and femur should be treated with amputation combined with multicytostatic treatment or immunotherapy and axial tumors with local resection and multicytostatic or immunologic treatment.     

Limb salvage using original low heat-treated tumor-bearing bone

Limb salvage, using original low heat-treated tumor-bearing bone and a conventional joint prosthesis, was done in six patients with malignant tumors of the proximal humerus (one patient with chondrosarcoma and five patients with osteosarcoma) and in six patients with tumor of the proximal femur (two patients with malignant spindle cell sarcoma and four patients with osteosarcoma). Wide excision of the lesion was done and the tumor and surrounding soft tissues were removed. The excised bone was treated with heat and the prosthesis was inserted into the treated bone and fixed with cement. This construct was reinserted into the original site and anchored to the host bone with a plate. The overall union rate of the low heat-treated bone with normal host bone was 91.7%, and the mean union time was 4.6 months (range, 3-7 months) after surgery. The functional result of the proximal femur and proximal humerus were 76.7% and 56.8%, respectively, using the Musculoskeletal Tumor Society functional evaluation system. Complications included hip dislocation in one patient, fracture of the low heat-treated bone in two patients, and absorption of the low heat-treated bone of the humerus in four of six patients. The 5-year survival rate of the low heat-treated tumor-bearing bone was 83.3% using Kaplan-Meier survival analysis. Based on the results of this study, limb salvage using original low heat-treated tumor-bearing bone seems to be effective in treating primary bone sarcoma with high survival and acceptable complication rates, circumventing the complications of allograft bone.     

Limb-salvage surgery in the treatment of osteosarcoma in skeletally immature individuals

Sacrifice of major growth plates during resection and fixed-length reconstruction of a limb in a skeletally immature child with osteosarcoma may result in a significant limb-length inequality as growth progresses. A limb-length discrepancy in the humerus may cause minor cosmetic problems but does not generally result in a significant functional deficit. In the lower extremity, tumors about the knee, including the distal femur and proximal tibia, usually present the dilemma of whether limb salvage by arthrodesis, osteoarticular allograft, or endoprosthetic replacement would result in a significant limb-length inequality and whether amputation of the extremity is a preferable procedure. The techniques of rotationplasty and an expandable endoprosthesis have been successfully used for treating skeletally immature patients with osteosarcoma of the distal femur. With regard to survival and function, the results obtained with these innovative methods are favorable compared with those of a high above-knee amputation.     

The prognosis in osteosarcoma

Summary Multifactorial analysis of patients with osteosarcoma of the distal femur and proximal tibia, recorded in the Swedish Cancer Registry during 1958 through 1968, disclosed a 5-year survival of 15.1% for femoral osteosarcomas and 38.1% for tibial tumours. The prognosis was better in adults than in children and better in males than in females. Tumour size, soft tissue involvement, the presence of pathological fracture and the duration of symptoms before treatment influenced the prognosis. The best treatment for the tibial lesions was high amputation alone, whilst for the femoral tumours primary ablative surgery was not superior to combined high-dose radiotherapy and delayed amputation. The main cause for the higher survival rate for tibial neoplasms seemed to be the fact that they were less advanced on admission than those of the distal femur. The findings emphasize the importance of early diagnosis and treatment for improved survival.A Comparative Multifactorial Analysis of Osteosarcoma of the Distal Femur and Proximal Tibia Recorded in the Swedish Cancer Registry 1958 through 1968     

Surgical treatment of the severely ischaemic leg: I. Survival rates

Over a 10-year period, 411 patients with atherosclerotic major artery disease causing severe ischaemia of the legs were treated by surgery. Their survival rate, assessed by the life table method, was 80 per cent at 1 year and 50 per cent at 5 years. Early and late survival rates were significantly worse in elderly patients, and in patients with extensive gangrene. Late survival rates were significantly worse in diabetics, and in patients with clinical myocardial ischaemia. Patients treated by arterial reconstruction showed a better survival rate than those treated by sympathectomy or amputation, though the latter groups contained more poor risk patients. Survival rates were not influenced by the technique of reconstruction.     

The surgical technique for hindquarter amputation. A report of 19 cases

The surgical technique for hindquarter amputation is described in a step-by-step manner. Since 1955 we have performed 19 such operations for eradication of malignant bone and soft tissue tumors in the pelvic, hip and upper thigh regions. Three hindquarter amputations were performed for local recurrence following initial wide excision. The overall 5-year survival rate for our 19 patients was 42.1 per cent. Malignant soft tissue tumors appear to have a much better 5-year survival rate than malignant bone tumors (60 per cent vs. 22.2 percent). We feel that surgery is still the treatment of choice. However, in the presence of proper indications, chemotherapy and radiotherapy should be added to surgery in order to prolong survival time and save lives.     

Limb-salvage treatment versus amputation for osteosarcoma of the distal end of the femur

A retrospective multi-institutional study of 227 patients with osteosarcoma of the distal end of the femur was done to compare rates of local recurrence, metastasis, and survival. Three cohorts of patients who had had either a limb-sparing procedure, an above-the-knee amputation, or disarticulation of the hip were compared. The results revealed prevalences of eight of seventy-three, nine of 115, and zero of thirty-nine as to local recurrence; forty-three of seventy-three, sixty-five of 115, and twenty-one of thirty-nine as to metastasis; and thirty-three of seventy-three, forty-eight of 115, and eighteen of thirty-nine as to death. Of the seventeen patients who had a local recurrence, sixteen died. In the limb-salvage group, eighteen patients required amputation, because of local recurrence in eight and other local complications in ten. The Kaplan-Meier estimates of the percentage of patients who survived and the percentage of patients without recurrent disease showed no difference among the three surgical groups (Mantel-Cox test statistic: p = 0.8) after a median length of follow-up of five and one-half years. Various covariant adjusted estimates yielded similar results. For the entire group of patients, the rate of continuously disease-free survival was 42 per cent, and the over-all rate of survival was 55 per cent at five years. It appears that, compared with above-the-knee amputation or disarticulation of the hip, the use of a limb-salvage procedure for osteosarcoma of the distal end of the femur did not shorten the disease-free interval or compromise long-term survival.     

Limb conservation for soft tissue sarcomas of the shoulder and pelvic girdles

Fifty-five patients with soft tissue sarcomas of the shoulder and pelvic girdles were treated between 1982 and 1987 with a consistent policy of limb conservation, using a wide variety of excisional and reconstructive surgical techniques and radical radiotherapy. Actuarial 5-year overall survival was 75 per cent for patients with low or intermediate grade tumours, and 38 per cent for those with high grade tumours (log rank test, P less than 0.05). Five-year local recurrence rates were 32 per cent for low or intermediate grade tumours, and 48 per cent for high grade tumours (log rank test, not significant). Multivariate analysis of the following risk factors for overall survival was performed: age, sex, tumour site, diameter, grade, inadequate surgical margins and local recurrence. Age over 55 years and high tumour grade emerged as independent prognostic variables for survival. Forequarter or hindquarter amputations were undertaken in seven of the 55 patients for local recurrence following previous limb-conserving surgery and radiotherapy. Local failure was not always salvaged by major amputation; satisfactory proximal tumour clearance was achieved in only two of seven patients undergoing major amputation; four of the seven patients developed stump recurrence, three of whom died with uncontrolled local disease. Meticulous attention to surgical and radiotherapeutic technique is required to minimize the incidence of local recurrence while maintaining satisfactory limb function.     

Rotationplasty for limb salvage in the treatment of malignant tumors at the knee. A follow-up study of seventy patients

Seventy patients who had a rotationplasty for treatment of a malignant tumor in the region of the knee (the femur or the tibia) between 1974 and 1987 were followed for two to thirteen years (mean duration of follow-up, four years). Forty-seven patients had a stage-IIB osteosarcoma; the remaining twenty-three patients had a malignant fibrous histiocytoma, a chondrosarcoma, a Ewing sarcoma, or a giant-cell tumor. The most severe postoperative complication was occlusion of the reanastomosed vessels (seven patients), leading to amputation proximal to the knee in three patients. Other complications were problems with wound-healing (eight patients), transient nerve palsy (five patients), irreversible nerve palsy (two patients), pseudarthrosis (four patients), and rotational malalignment (one patient). Late complications included eight fractures, two infections, two delayed unions, and one lymphatic fistula. More than half of the patients were free of complications related to the operative procedure. Forty-four of the patients who had a stage-IIB osteosarcoma could be followed, and their data were analyzed for survival statistics. These patients had a 58 percent rate of disease-free survival and a 70 per cent rate of over-all survival. One patient had a local recurrence five years after the operation.     

四肢Ⅱ期骨肉瘤的化疗效果评价

目的 对四肢骨肉瘤患者实施化疗的效果以及与生存率的关系进行总结.方法 1997年7月至2007年7月采用新辅助化疗及手术治疗ⅡB期骨肉瘤患者296例,其中男性184例,女性112例,年龄7～65岁.其中股骨近端10例,股骨干部7例,股骨远端148例,胫骨近端80例,胫骨远端5例,腓骨11例,肱骨33例,桡骨远端2例.外科分期(Enneking分期):6例为ⅡA期,290例为ⅡB期.对所有病例进行术前化疗反应评估,72例进行肿瘤坏死率分析.结果 296例患者平均随访时间47个月,出现远处转移98例,占33.1%.对术前化疗反应明显有效的103例患者中,15.5%出现转移;部分有效的145例患者中,31.0%出现转移;术前化疗无效的48例患者77.1%出现转移.在坏死率分析研究中,化疗后肿瘤体积明显缩小、肿瘤边界变清晰的病例,肿瘤坏死率明显升高.结论 骨肉瘤一旦诊断明确,应尽早给予化疗,化疗效果良好的患者,全身转移的可能性减小,无瘤生存率高.     

The Surgical Technique for Hindquarter Amputation: A Report of 19 Cases

The surgical technique for hindquarter amputation is described in a step-by-step manner. Since 1955 we have performed 19 such operations for eradication of malignant bone and soft tissue tumors in the pelvic, hip and upper thigh regions. Three hindquarter amputations were performed for local recurrence following initial wide excision. The overall 5-year survival rate for our 19 patients was 42.1 per cent. Malignant soft tissue tumors appear to have a much better 5-year survival rate than malignant bone tumors (60 per cent vs. 22.2 per cent). We feel that surgery is still the treatment of choice. However, in the presence of proper indications, chemotherapy and radiotherapy should he added to surgery in order to prolong survival time and save lives.     

Marginal resection for osteosarcoma with effective preoperative chemotherapy

Objective: To present the clinical results of marginal resection with effective preoperative chemotherapy for treatment of osteosarcoma. Methods: Thirty‐eight patients (20 male and 18 female, average age 17 years), underwent marginal resection after confirmation of effective preoperative chemotherapy between 1999 and 2008 and the results were analyzed retrospectively. The distal femur was involved in 22 cases, proximal tibia in 11, proximal humerus in 4, and proximal fibula in 1. Thirty‐seven patients were stage IIB and one IIIB. Twenty‐nine patients were treated with the DIA, and 9 with the MMIA protocol. Twenty‐one patients underwent tumor resection and bone allograft transplantation. The epiphysis was preserved in 9 patients, and not in the other 12. Eleven patients underwent tumor resection and prosthetic replacement, and 4 tumor resection with autograft implantation. One patient underwent tumor resection and allograft with preservation of the epiphysis; another underwent marginal tumor resection only. Results: All patients received effective preoperative chemotherapy. At a median follow‐up of 52 months, local recurrence had developed in one patient (2.6% local recurrence rate). Pulmonary metastases developed in 9 patients (23.7%). Five patients died of metastases, one died of intracranial hemorrhage due to thrombocytopenia caused by postoperative chemotherapy. The overall 2‐year survival rate was 87.3%, and event‐free survival rate 75.5%. The overall 5‐year survival rate was 74.7%, and event‐free survival rate 60.8%. Excellent to good function of affected limbs was achieved in 60.5%. Conclusions: With careful preoperative evaluation and effective preoperative chemotherapy marginal resection of osteosarcoma can produce good results. Marginal resection of osteosarcoma should be performed by an experienced surgeon who is familiar with the limb salvage rules for osteosarcoma.     

Energy cost during gait in osteosarcoma patients after resection and knee replacement and after above-the-knee amputation

We determined the energy cost during gait by measuring the oxygen consumption of twenty-six patients after treatment for osteosarcoma about the knee. Fourteen had had an en bloc resection of the distal end of the femur and proximal end of the tibia followed by segmental replacement with a custom-made knee prosthesis and twelve had had an above-the-knee amputation followed by fitting with an artificial limb. Comparisons of free-walking velocity, oxygen consumption per meter traveled, and per cent of maximum aerobic capacity used during walking demonstrated that patients with resection and prosthetic knee replacement had a lower energy cost during gait.     

Soft-tissue sarcomas of the proximal lower extremity

Of 54 patients with soft-tissue sarcomas of the proximal part of the lower extremity, 2 patients (4%) were treated with amputation, while 52 patients (96%) were treated with limb-preserving resection. Adjuvant postoperative irradiation was applied selectively when the minimum margin was less than 2 cm (22 patients). Technical improvements in exposure, resection of involved vessels or nerve, and preservation of function permitted a high rate of limb salvage with satisfactory function. At a median follow-up of 30 months for those subjects still alive, the 5-year disease-free survival rate was 65%, and only 3 patients (6%) had had a local recurrence.     

Amputation for Tumor of the Upper Arm

In a 10-year period 35 patients underwent a proximal amputation of the upper limb because of a malignant tumor. in 27 patients a forequarter amputation was made, in one a humeroscapular disarticulation and in seven an amputation through the humerus. the observed 5-year survival was 23 per cent. Twelve out of 23 patients followed for at least 3 years also survived 3 years. Fifteen living patients were questioned concerning prosthetic use and social and psychologic factors. Only three patients used a functional (mechanical) prosthesis and only five used a cosmetic prosthesis. the other seven patients rejected the use of a prosthesis. Half of the patients had the same occupation postoperatively as preoperatively. Activities of daily living did not constitute any major problem. One of three housekeepers needed daily help. One patient seemed to have suffered obvious psychologic damage.     

Therapie und Prognose des kindlichen Osteosarkoms

Zusammenfassung In einer interklinischen Studie werden 126 Fälle von kindlichen Osteosarkomen analysiert. Es findet sich eine zunehmende Häufigkeit bis zum 15. Lebensjahr bei geringem Überwiegen des männlichen Geschlechtes. Das kindliche Osteosarkom bevorzugt den distalen Femur, die proximale Tibia und den proximalen Humerus. Die Behandlung wurde — bedingt durch die verschiedenen Kooperationszentren — uneinheitlich durchgeführt. Überlebende finden sich in allen Altersgruppen. Multiple Metastasen — meist in den Lungen, aber auch im Skelet — treten gehäuft innerhalb des 1. Jahres und fast immer innerhalb der ersten 2 1/2 Jahre nach Diagnosestellung auf. Zur Prognosebeurteilung genügt daher die 21/2-Jahres-Grenze. Die anscheinend besseren Ergebnisse nach frühzeitiger Amputation lassen diese Methode beim kindlichen Osteosarkom empfehlenswert erscheinen. Mit der alleinigen Strahlentherapie konnten keine Heilungen erzielt werden. Zusätzlich zur frühzeitigen Radikalbehandlung läßt die intensive prophylaktische Chemotherapie bessere Resultate erwarten.

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Treatment and prognosis of osteosarcoma in childhood

Summary 126 osteosarcoma under the age of 15 years are followed up in an interclinical study. There is a steady increase of tumor incidence towards the 15th year with a slight male preponderance. The main sites of the tumor are the distal femur followed by the proximal tibia and humerus. Evidence of multiple metastases is most often present in the lungs, less often in the skeleton. Nearly always metastases became evident within 2 1/2 years after diagnosis (98%). Therefore the 2 1/2-year disease—free survival rate seems to be sufficient for prognostic evaluation. The over all 2 1/2-year survival rate was 17,5%. Though the different methods of treatment are not statistically valid, the best results can be expected after early amputation. By radiotherapy alone no cure has been achieved. Survivals were seen at any age and at any site of long bones (distal femur, proximal tibia, humerus, femur, distal radius). Prognosis of osteosarcoma in the childhood is similar to that of the adult group.

     

Surgical aspects of subungual malignant melanomas. The Scottish Melanoma Group.

The incidence, treatment, and survival of subungual malignant melanomas in Scotland is reviewed from the Scottish Melanoma Group database. Between 1979 and 1989, 100 cases of subungual melanoma were identified (2.8% of all malignant melanomas in Scotland). The tumors tended to be locally advanced at the time of presentation (mean Breslow depth, 4.7 mm +/- 3.0 mm), and this is reflected in an overall 5-year survival of 41%. There was no difference in the survival of patients treated with local/proximal interphalangeal (PIP) joint amputation compared with those having more proximal amputations. Because nearly 70% of these tumors arose on the thumb or hallux, it is concluded that, provided adequate clearance could be obtained, less radical excision should be performed for these lesions to maintain maximum function.     

Immunologic studies concerned with high dose radiotherapy for osteosarcoma (author's transl)]

The 5-year cumulative survival rate was measured in 28 cases of osteosarcoma treated with high dose radiation since 1969 is 48.8% in our clinic. It can be said that high dose radiotherapy has a significant survival effect compared to early amputation therapy for the patient with osteosarcoma. The difference of the prognosis between both therapies may be related to immunological reactions. In order to obtain further information on this possibility, experimental studies on mice suffering from tumors have been performed. Results revealed that spleen cell migration inhibition reaction, as a specific immunity, became negative and anti-tumor properties were eliminated as a results of the amputation of the limb bearing the tumor. Also, when BCG as well as irradiated tumor cells were administered to tumor-afflicted mice, an improved rate of survival among the mice was observed. As a result of the study of patients with osteosarcoma that has been treated with high dose radiation related to changes in their immunity, it was disclosed that there was a marked tendency to diminution in peripheral blood lymphocytes or T cells in cases with poorer prognoses. In cases of long survival, both showed high values. Lymphoblastgenesis by PHA and PWM showed higher values in cases with better prognoses than in those with poor prognoses. Furthermore, in many of the cases in which the tuberculin skin reaction became negative, a short survival period was noted.     

Adenocarcinoma of the head of the pancreas: effects of surgical and nonsurgical therapy on survival--a ten-year experience

A retrospective analysis of all patients treated for adenocarcinoma of the head of the pancreas from 1989 to 1998 was performed. Excluded were cancers in the body and tail, cystic neoplasms, ampullary tumors, and cancers of the duodenum and bile ducts. One hundred forty-five patients were reviewed, and 43 patients underwent pancreaticoduodenectomy. Data collected included the stage, lymph node status, surgical margins, adjuvant therapies, and survival. Statistical analysis was performed with Cox's Proportional Hazards Analysis and Log-Rank Life Table Analysis. The surgical population had a 21 per cent 3-year survival rate and a 7 per cent operative mortality rate. Median survival was: 1) the resection group versus no resection was 13.5 versus 3.1 months; 2) adjuvant therapy versus no therapy after resection was 16.1 versus 5.1 months; and 3) chemoradiation therapy versus no therapy for unresectable disease was 5.3 versus 1.8 months. The presence of positive surgical margins was found in 33 per cent of the surgical specimens and carried an increased mortality hazard ratio of 3.1. Patients with negative lymph nodes had a 15 per cent 5-year survival, versus 0 per cent with positive nodes. Seventy-three per cent of those resected had a T2 lesion, and 46 per cent of patients presented with metastatic disease. Surgical resection and adjuvant therapy significantly improves survival in patients with adenocarcinoma of the head of the pancreas. All patients who underwent resection as part of their therapy showed extended survival compared with chemoradiation therapy alone. Adjuvant chemoradiation improved survival when compared with surgery alone. Multimodality treatment in carcinoma of the head of the pancreas provides the best treatment option. However, better adjuvant therapies are needed.     

Endoprosthetic replacement following resections of malignant tumors of the extremities (author's transl)]

Due to advances in chemotherapy and endoprothetics, amputation is increasingly being replaced by local resectioning in malignant tumors. While suitable implantations for bridging defects in the proximal humerus and proximal femur are available, prostheses for resectioned tumors in the knee area have not yet been fully developed. From 1966 to 1978, 77 endoprostheses were implanted in 29 primary bone tumors, 3 malignant soft-tissue tumors and 45 bone metastases. There were 43 endoprostheses of the proximal femur, 31 endoprostheses of the proximal humerus and 3 special endoprostheses of the knee region. In most cases, eliminating the tumor radically was successful and a functional extremity was retained.