Limb salvage in extremity soft-tissue sarcoma: combined modality therapy

Thirty-two consecutive patients with high-grade soft-tissue sarcoma of an extremity were treated preoperatively with concomitant intra-arterial infusion of Adriamycin (doxorubicin) (10 mg/m2 daily for 10 days) and radiotherapy (2500 rad [25 Gy] in 10 fractions in 2 weeks). En bloc resection was then performed. Postoperatively, depending on the surgical specimen findings, radiotherapy was given to a dose ranging from 5000 rad (50 Gy) in 5 weeks to 6000 rad (60 Gy) in 6 weeks equivalent continuous schedules. No residual tumor was found in 28% of the surgical specimens and only minimal tumor in 41%. A functionally intact limb was preserved in 30 patients (94%). Local recurrence developed in one patient (3%). The actuarial overall survival at three years was 70% and disease-free survival 57%.     

Hypofractionated adjuvant radiation therapy of soft-tissue sarcoma achieves excellent results in elderly patients

Objective:

Adjuvant radiation therapy (RT) is an essential part of combined limb-sparing treatment of soft-tissue sarcoma (STS). Elderly or medically unfit patients often have difficulty in completing 6–7 weeks of standard fractionated daily treatment. Our aim was to evaluate the efficacy of a hypofractionated adjuvant approach with RT for STS in elderly and debilitated patients.

Methods:

21 elderly patients were treated with a short course of adjuvant RT (39–48 Gy, 3 Gy per fraction) for STS. The medical records of the patients were retrospectively reviewed for local or distant recurrence and side effects of RT.

Results:

At a mean 26 months of follow-up, three local recurrences (14%) were detected. Eight patients (38%) had lung metastases during the observed period. Three of them died from metastatic disease. The hypofractionated radiation was well tolerated with minimum long-term side effects.

Conclusion:

Hypofractionated adjuvant radiation appears to be an effective treatment in terms of local control in elderly and debilitated patients.

Advances in knowledge:

The results of this study might provide an alternative to commonly used standard fractionation of radiotherapy in sarcoma patients.Soft-tissue sarcoma (STS) is a relatively rare disease. The age-adjusted incidence rate is 3.3 per 100 000 males and females per year. From 2005 to 2009, the median age at diagnosis for cancers of the soft tissue was 58 years. Approximately 16.1% were diagnosed between 65 and 74, 16.3% between 75 and 84 and 7.3% at 85+ years old [1].The modern approach to high-grade limb STS in adults is based on limb-sparing surgery followed by radiation therapy (RT). The benefit of RT in terms of local control was documented in two randomised trials [2,3]. The indications for pre-operative or post-operative chemotherapy are not sufficiently clear at this juncture. Adjuvant RT is an essential part of combined limb-sparing treatment of STS. The recommended dose of radiation lies in the range of 60 Gy in standard fractionation of 1.8–2.0 Gy. Elderly or medically unfit patients often have difficulty in completing 6–7 weeks of daily treatment. Moreover, a prolonged course of radiation may be interrupted by acute side effects, which sometimes demands further extension of the overall course or even discontinuation of treatment.We retrospectively studied the rate of local control and distant metastases in elderly patients with STS treated by short-course adjuvant radiation.     

Preoperative radiation therapy to a complex retroperitoneal soft-tissue sarcoma: a case study.

Due to their location, retroperitoneal sarcomas tend to present late and with a large size, thus limiting any potential surgical procedure. The inability to achieve local control is the most common cause of treatment failure. This case study describes a challenging example of preoperative radiation therapy for a patient with a retroperitoneal soft-tissue sarcoma. Three-dimensional treatment planning for an asymmetric multibeam arrangement was utilized, with the goal of achieving complete resection at surgery, and thus an improved prognosis, while avoiding high dose to sensitive structures.     

Re-irradiation of soft-tissue sarcoma.

Re-irradiation for local recurrence of malignancy after radical radiotherapy is of proven benefit at head and neck sites but has seldom been used elsewhere. This paper reports a series of 10 patients re-irradiated with external-beam techniques for local recurrence of soft-tissue sarcoma of the limb and limb girdle following initial limb conserving management with surgery and radiotherapy (dose range 33-60 Gy). Median survival was 14 months following re-treatment. Two cases received treatment with high-energy electrons and the rest with megavoltage photons. Five patients re-treated with radical intent (dose range 40-60 Gy) had a median survival of 36 months and median recurrence-free survival of 16 months. All five patients treated palliatively (dose range 12-50 Gy) have died, although two demonstrated local control until death. Acute reactions were not severe. Radionecrosis was seen in one patient who was re-irradiated twice (total dose 145 Gy) and subsequently required amputation. One other case required amputation for persistent local disease, but in the remaining eight, limb conservation was achieved. Re-irradiation of soft-tissue offers good local control and may avoid amputation.     

Radiation-induced soft-tissue and bone sarcoma.

From the records of Memorial Hospital of the past 50 years, 47 cases with an established diagnosis of radiation-induced sarcoma were identified and divided into two groups: the first included 20 cases of soft-tissue sarcoma arising from irradiated tissues, and the second comprised 27 cases of bone sarcoma arising from normal bones in the irradiated field. Medians for the latent periods from irradiation to diagnosis of bone and soft-tissue sarcoma were 11 and 12, years, respectively. In bone sarcomas, the latent period was longer after larger radiation doses and children appeared to be more susceptible to cancer induction than adults. Criteria for establishing the diagnosis of radiation-induced sarcoma and the magnitude of the risk of bone sarcoma are discussed.     

Immobilization and image-guidance methods for radiation therapy of limb extremity soft tissue sarcomas: Results of a multi-institutional survey

Radiation therapy for limb-extremity soft tissue sarcoma (STS) requires accurate, reproducible dose delivery. However, patient positioning is challenging and there is a lack of existing guidelines to assist institutional standardization. Therefore, we conducted a multi-institutional international survey of STS immobilization, image guidance methods, and treatment protocols to investigate current practice. Seventy-three UK radiotherapy centers and 15 hospitals in 7 other countries completed a questionnaire on STS immobilization and image-guidance procedures. Specifically, the survey collated information on the current usage of immobilization equipment, including custom devices, patient setup tolerances, the use of written protocols, the modality and frequency of image guidance, the method of treatment, allocated treatment times, and the application of surgical clips. Multiple combinations of immobilization devices were reported. In the UK, 12%, 40%, 30%, 12%, and 5% use 1, 2, 3, 4, and 5 types of device for lower limb STS. Vacuum bag plus either foot or ankle support was most common (66%). Of 15 international centers, 27%, 60%, 7%, 0%, 7% use 1, 2, 3, 4, 5 devices, with vacuum bags (73%) and thermoplastic (47%) predominant, similar to UK values of 77% and 52%. For image guidance, in the UK, 37% use kV planar, 34% use MV planar, and 16% use cone-beam CT for the first 3 fractions and then weekly. Internationally, daily imaging was more prevalent with 33% using kV planar, 7% MV planar, and 40% cone-beam CT daily. Custom devices plus combinations of devices, along with 5- and 10-mm set-up tolerances, were most commonly reported. Less than half of centers have written treatment protocols. Conventional treatment is most common in the UK, with only 42% using conformal techniques. Treatment is allocated between 10 and 30 minutes. Twenty-six percent of UK centers and 53% of international centers use surgical clips. Across treatment centers, there is no consistent approach to STS immobilization, image-guidance methods, or treatment protocols assessed by this survey. A wide variety of immobilization devices and configurations are utilized, and the frequency and modality of imaging are similarly diverse. In the absence of guidelines, the creation of an online repository of example immobilization techniques could enable centers to compare a diversity of cases. The availability of a forum for viewing and discussing a range of cases could potentially lead to improved patient setup and reduce the time taken to devise an individual immobilization strategy.     

Limb-sparing management with surgical resection,external-beam and intraoperative electron-beam radiation therapy boost for patients with primary soft tissue sarcoma of the extremity

Background or purpose

A joint analysis of data from three contributing centres within the intraoperative electron-beam radiation therapy (IOERT) Spanish program was performed to investigate the main contributions of IORT to the multidisciplinary treatment of high-risk extremity soft tissue sarcoma (STS).

Methods and materials

Patients with an histologic diagnosis of primary extremity STS, with absence of distant metastases, undergoing limb-sparing surgery with radical intent, external beam radiotherapy (median dose 45 Gy) and IOERT (median dose 12.5 Gy) were considered eligible for participation in this study.

Results

From 1986–2012, a total of 159 patients were analysed in the study from three Spanish institutions. With a median follow-up time of 53 months (range 4–316 years), 5-year local control (LC) was 82?%. The 5-year IOERT in-field control, disease-free survival (DFS) and overall survival (OS) were 86, 62 and 72?%, respectively. On multivariate analysis, only microscopically involved margin (R1) resection status retained significance in relation to LC (HR 5.20, p?p?=?0.001) and higher IOERT dose (≥?12.5 Gy; HR 0.32, p?=?0.02) retained a significant association in multivariate analysis.

Conclusion

From this joint analysis emerges the fact that an IOERT dose ≥?12.5 Gy increases the rate of IOERT in-field control, but DFS remains modest, given the high risk of distant metastases. Intensified local treatment needs to be tested in the context of more efficient concurrent, neo- and adjuvant systemic therapy.     

Immobilization devices for intensity-modulated radiation therapy (IMRT).

Three-dimensional conformal radiation therapy (3DCRT) and intensity-modulated radiation therapy (IMRT) plans show radiation dose distribution that is highly conformal to the target volume. The successful clinical implementation of these radiotherapy modalities requires precise positioning of the target to avoid a geographical miss. Effective reduction in target positional inaccuracies can be achieved with the proper use of immobilization devices. This paper reviews some of the immobilization devices that have been used and/or have the potential of being used for IMRT. The immobilization devices being reviewed include stereotactic frame, Talon system, thermoplastic molds, Alpha Cradles, and Vac-Lok system. The implementation of these devices at various anatomical sites is discussed.     

Gallium imaging in metastatic and recurrent soft-tissue sarcoma.

Fifty-six patients with metastatic or recurrent soft-tissue sarcoma were evaluated by 67Ga-citrate imaging. Prior to entry on the therapy protocol, 52/56 (93%) patients had true-positive 67Ga studies. Two of four patients with liposarcoma, one of twelve with leiomyosarcoma and one with an epithelioid sarcoma had false-negative studies; 89/105 disease sites (85%) were 67Ga positive, including 100% of pleural lesions, 94% in bone, 88% in the abdomen, 85% in soft tissue, 78% in lung parenchyma and 56% of liver metastases. There was significant association between 67Ga avidity and tumor grade with the exception of mesothelioma. No relationship was seen between 67Ga avidity and tumor cell type, disease site or lesion size. Following therapy, 67Ga correctly identified 11/12 sites of active disease in 8/9 patients. Mean pre- and post-therapy 67Ga avidity scores did not differ significantly. Gallium-67 appears to have an important role in the evaluation of patients presenting with either primary or metastatic soft-tissue sarcoma.     

Real-time computer verification for radiation therapy treatment machines.

A computer based verification system which monitors the operation of a 4-MV linear accelerator is described. Fourteen parameters can be checked for proper alignment prior to irradiation. A training simulator was also built to minimize interference with treatment schedules and to provide technicians with experience in using the system during the developmental stages of the project.     

First place 1989 Alpha Cradle Award winner. Positioning and immobilization device for patients receiving radiation therapy for carcinoma of the breast

Careful treatment planning and dose calculation, combined with effective positioning and immobilization, may improve the probability of tumor control. Modern radiation therapy equipment has had a significant impact on the accuracy of dose calculation and delivery. However, the problems of patient repositioning and immobilization, which may represent the area of the greatest variance in precise treatment delivery, still need much improvement. On this premise, many site specific repositioning and immobilizing devices have been developed in our institution for radiation therapy. Alpha Cradles have been used for positioning of patients undergoing irradiation for carcinoma of the breast at our institution for several years but did not provide adequate support for the arm. A modification of an Alpha Cradle was developed specifically for breast treatments and is described in this report. The modification, which is easily made, consists of a mold which conforms tightly to the arm and allows minimal variation in repositioning of the arm. A handle, built into the device, offers the patient a comfortable resting place for the hand and also fixes the orientation of the hand during the treatments. This device offers a very comfortable support for the elevated arm and greatly improves the accuracy of repositioning the patient.     

鼻咽癌调强放疗与常规放疗患者生存质量的初步观察

目的 比较鼻咽癌患者调强放疗与常规放疗的急慢性反应和生存质量。方法 系统分析2008年8月至2010年9月在宁波市李惠利医院行常规放疗及调强放射治疗(IMRT)的初治鼻咽癌患者91例,分为IMRT组(35例)和常规放疗组(56例)。常规放疗采用面颈联合野+颈切线野及耳前野+颈部电子线野,靶区剂量2.0 Gy/次,35次,共70 Gy;调强放疗设定9个共面野,靶区剂量2.12 Gy/次,33次,共69.96 Gy。比较IMRT和常规放疗患者的急性不良反应如口干、吞咽疼痛、吞咽困难、皮肤和黏膜反应等;晚期放射损伤如吞咽困难、张口困难、甲状腺功能低下、视力及听力下降、皮肤损伤、皮下组织纤维化、脊髓炎、脑损伤等方面。结果 与常规组相比,IMRT组的急性不良反应有不同程度的减轻,口干、吞咽疼痛、吞咽困难、皮肤反应和黏膜反应等的发生率较低(χ²=85.73、 56.03、 26.58、69.28和55.99,P<0.05);晚期损伤中口干、吞咽困难、味觉改变、张口困难、皮肤损伤等方面显著减轻(χ²=37.95、7.48、9.49、9.49和11.87, P<0.05),而听力下降程度、视力损伤、脑损伤等的发生率差异无统计学意义,可能与随访时间较短有关。结论 相对于常规放疗,IMRT技术能够减轻急性不良反应,并减少晚期损伤发生率,改善患者的生存质量。     

18F-FDG PET for the diagnosis and grading of soft-tissue sarcoma: a meta-analysis.

PET using (18)F-FDG is increasingly used for the diagnosis and grading of tumors. Several studies have been performed that evaluate the diagnostic and grading performance of (18)F-FDG PET for soft-tissue sarcoma, but each study has had a limited sample size. Therefore, we undertook a comprehensive meta-analysis of the evidence. METHODS: Relevant studies were identified from MEDLINE and EMBASE. Diagnostic and grading performance were evaluated for qualitative visualization; standard uptake value (SUV, cutoffs of 2.0 and 3.0); and metabolic rate of glucose (MRG, cutoff of 6.0 micro mol/100 g/min). Quantitative data synthesis included independent weighting of sensitivity and specificity, construction of summary receiver operating characteristic curves, and pooled analyses. RESULTS: The meta-analysis included 15 studies with 441 soft-tissue lesions (227 malignant, 214 benign). For diagnosis of malignant versus benign lesions, typical pairs of sensitivity and specificity estimates from the summary receiver operating characteristic curves were 92% and 73% for qualitative visualization; 87% and 79% for SUV 2.0; 70% and 87% for SUV 3.0; and 74% and 73% for MRG 6.0. Diagnostic performance was similar for primary and recurrent lesions. By qualitative interpretation, (18)F-FDG was positive in all intermediate/high-grade tumors (95% confidence interval [CI], 97.3%-100%), 74.4% (95% CI, 58.6%-85.9%) of low-grade tumors, and 39.3% (95% CI, 29.1%-50.3%) of benign lesions (including 11 of 12 inflammatory lesions). Using an SUV cutoff of 2.0, respective rates were 89.4% (95% CI, 79.4%-95.6%), 33.1% (95% CI, 15.6%-55.3%), and 19.1% (95% CI, 10.6%-30.5%). Limited data on comparisons with MRI and CT showed no differences against (18)F-FDG PET in diagnosing recurrent and metastatic disease. CONCLUSION: (18)F-FDG PET has very good discriminating ability in the evaluation of both primary and recurrent soft-tissue lesions. (18)F-FDG PET may be helpful in tumor grading but offers inadequate discrimination between low-grade tumors and benign lesions.     

Interstitial brachytherapy vs. intensity-modulated radiation therapy for patients with cervical carcinoma not suitable for intracavitary radiation therapy

PurposeInterstitial brachytherapy (IBT) is the standard alternative treatment for patients with cervical carcinoma not suitable for intracavitary radiotherapy. There is an emerging belief that intensity-modulated radiotherapy (IMRT) has the potential to replace IBT. We aimed to compare the dosimetry achieved by IBT and IMRT in such patients.Methods and MaterialsThe CT imaging data, previously used for IBT planning of 12 patients with cervical carcinoma, were transferred to IMRT planning system to generate parallel IMRT plans. Prescribed dose to the planning target volume (PTV) was 20 Gy delivered in 2-weekly high-dose-rate fractions of 10 Gy each with IBT (biologically equivalent dose [BED₁₀] 40 Gy) and 33 Gy/13 fractions/2.5 wk with IMRT (BED₁₀ 41 Gy). For comparison, dose–volume parameters for target and organs at risk were recorded and expressed in terms of BED₁₀ and BED₃, respectively.ResultsFor PTV, the mean D₉₅ (dose received by 95% of PTV) was better with IBT (57.16 Gy vs. 41.47 Gy, p = 0.003). The mean conformity index was 0.94 and 0.90 with IBT and IMRT, respectively (p = 0.034). IBT delivered significantly reduced doses to 1.0 cc (D_max), 5.0 cc (D_{5 cc}), 50% (D₅₀), and 75% (D₇₅) of bladder volume as compared with IMRT. The mean rectal D_max was significantly better with IBT as compared with IMRT (54.64 Gy vs. 62.63 Gy, p = 0.02).ConclusionsIBT provides superior PTV coverage and organs at risk sparing to IMRT. Thus, IBT remains the standard treatment for patients with cervical carcinoma unsuitable for intracavitary radiotherapy.     

Comparison of three IMRT inverse planning techniques that allow for partial esophagus sparing in patients receiving thoracic radiation therapy for lung cancer.

The purpose of this study is to compare 3 intensity-modulated radiation therapy (IMRT) inverse treatment planning techniques as applied to locally-advanced lung cancer. This study evaluates whether sufficient radiotherapy (RT) dose is given for durable control of tumors while sparing a portion of the esophagus, and whether large number of segments and monitor units are required. We selected 5 cases of locally-advanced lung cancer with large central tumor, abutting the esophagus. To ensure that no more than half of the esophagus circumference at any level received the specified dose limit, it was divided into disk-like sections and dose limits were imposed on each. Two sets of dose objectives were specified for tumor and other critical structures for standard dose RT and for dose escalation RT. Plans were generated using an aperture-based inverse planning (ABIP) technique with the Cimmino algorithm for optimization. Beamlet-based inverse treatment planning was carried out with a commercial simulated annealing package (CORVUS) and with an in-house system that used the Cimmino projection algorithm (CIMM). For 3 of the 5 cases, results met all of the constraints from the 3 techniques for the 2 sets of dose objectives. The CORVUS system without delivery efficiency consideration required the most segments and monitor units. The CIMM system reduced the number while the ABIP techniques showed a further reduction, although for one of the cases, a solution was not readily obtained using the ABIP technique for dose escalation objectives.