Soft tissue sarcomas: long-term aspects of combined modality treatment

In de gecombineerde behandeling van weke-delen sarcomen is chirurgie de hoeksteen van een succesvolle behandeling. Hyperthermische geïsoleerde perfusie van een extremiteit met Tumor Necrosis Factor alpha (TNFa) en melphalan was een doorbraak voor het behoud van de extremiteit bij primair irresectabele weke-delen sarcomen. Na deze behandeling zijn er nog drie risicovolle tijdsperioden voor amputatie ten gevolge van uitgebreide necrose, lokaal recidief en ernstige ischemische schade van een extremiteit. Adjuvante radiotherapie is aangewezen wanneer de resectiemarges krap zijn of microscopisch niet vrij en lijkt zelfs een meerwaarde te hebben na een microscopisch vrije resectie. Alhoewel de levenskwaliteit van de in leven zijnde patiënten die een weke-delen sarcoom hebben gehad alleen in fysiek functioneren verschilt van een referentiegroep, lijdt een vijfde van hen aan posttraumatische stress respons symptomen (PTSS). Een amputatie, de behandelingskeuze voor de perfusie door de arts eerder dan door de patiënt en lage tevredenheid over de uitgevoerde behandeling beïnvloedden de kwaliteit van leven negatief. Patiënten met een uitgebreid lokaal weke-delen sarcoom lopen een hoog risico om gediagnosticeerd te worden met een andere primaire tumor. De overleving van patiënten met een niet-gemetastaseerd weke-delen sarcoom was significant minder als patiënten al een andere primaire tumor vóór de diagnose van het weke-delen sarcoom hadden. Biologische beeldvorming lijkt een waardevol instrument om inzicht te krijgen in de effecten van de tumorbehandeling. Andere ‘radicale’ verschuivingen in paradigma’s van de kankerbiologie en de gevolgen voor de patiënt, zowel op oncologisch als functioneel gebied, zullen in de toekomst de behandeling van weke-delen sarcomen bepalen. Een ‘radicale’ operatie zal niettemin de eerste stap in een succesvolle kankerbehandeling blijven, meer en meer in een ‘combined modality’ setting met pre- of postoperatieve radiotherapie en/of (neo)adjuvante chemotherapie.

Oxaliplatin-dacarbazine combination chemotherapy for the treatment of advanced soft tissue sarcoma of the limbs

<p>Abstract</p> <p>Background</p> <p>This study was designed to explore the feasibility, safety, and outcomes of pre-operative oxaliplatin-dacarbazine combination therapy for the treatment of advanced soft tissue sarcoma (STS) of the limb.</p> <p>Patients and Methods</p> <p>Between November 2005 and November 2008, 31 patients with advanced limb STS classified with stage IV STS were randomly assigned into experimental or control groups, and both were given 2 cycles of chemotherapy before undergoing surgery. The regimen for the experimental group was oxaliplatin (120 mg/m², d₁) in combination with dacarbazine (175 mg/m², d₁₃), while that for the control group was a standard vincristine, epirubicin, cyclophosphamide therapy. Operations were carried out four weeks after the second chemotherapy cycle, followed by another 24 more chemotherapy cycles of the previous regimen.</p> <p>Results</p> <p>Following preoperative chemotherapy, the experimental group exhibited a significant improvement in tumor regression compared to controls. Both regimens were well-tolerated, and no significant differences in adverse reactions were noted. At a median follow-up of 24 months, 28 patients were still alive and had normal limb function. The progression free survival rate of the experimental group was significantly higher than that of the control group (10/15 vs. 4/16, <it>p </it>< 0.05).</p> <p>Conclusion</p> <p>Oxaliplatin- dacarbazine neoadjuvant/adjuvant chemotherapy improved the prognosis of patients with advanced limb STS in comparison with vincristine, epirubicin, cyclophosphamide combination therapy.</p

Long-Term Locoregional Vascular Morbidity After Isolated Limb Perfusion and External-Beam Radiotherapy for Soft Tissue Sarcoma of the Extremity

Background: Isolated limb perfusion (ILP) with tumor necrosis factor alpha (TNF-alpha) and melphalan, followed by delayed surgical resection and adjuvant external-beam radiotherapy is a limb salvage treatment strategy for locally advanced soft tissue sarcomas. The long-term vascular side effects of this combined procedure were evaluated. Methods: Thirty-two patients were treated for a locally advanced sarcoma of the upper (n = 5) or lower limb (n = 27). All patients underwent a noninvasive vascular work-up. Results: Five patients underwent a leg amputation, in two cases due to critical leg ischemia 10 years after ILP. With a median follow-up of 88 (range, 17-159) months, none of the patients with a salvaged lower leg (n = 22) experienced peripheral arterial occlusive disease. Ankle-brachial index (ABI) measurements in the involved leg (median, 1.02; range, .50-1.20) showed a significant decrease compared with the contralateral leg (median, 1.09; range, .91-1.36, P = .001). Pulsatility index (PI) was decreased in the treated leg in 17 of 22 patients at the femoral level (median, 6.30; range, 2.1-23.9 vs. median, 7.35; range, 4.8-21.9; P = .011) and in 19 of 20 patients at popliteal level (median, 8.35; range, 0-21.4 vs. median, 10.95; range, 8.0-32.6; P <.0005). In patients with follow-up of > 5 years, there was more often a decrease in ABI (P = .024) and PI at femoral level (P = .011). Conclusions: ILP followed by resection and external-beam radiotherapy can lead to major late vascular morbidity that requires amputation. Objective measurements show a time-related decrease of ABI and femoral PI in the treated extremity

Isolated Limb Perfusion and External Beam Radiotherapy for Soft Tissue Sarcomas of the Extremity: Long-Term Effects on Normal Tissue According to the LENT-SOMA Scoring System

BACKGROUND: With the combined treatment procedure of isolated limb perfusion (ILP), delayed surgical resection and external beam radiotherapy (EBRT) for locally advanced soft tissue sarcomas (STS) of the extremities, limb salvage rates of more than 80% can be achieved. However, long-term damage to the healthy surrounding tissue cannot be prevented. We studied the late effects on the normal tissue using the LENT-SOMA scoring system. PATIENTS AND METHODS: A total of 32 patients-median age 47 (range 14-71) years-were treated for a locally advanced STS with ILP, surgical resection and often adjuvant 60-70 Gy EBRT. After a median follow-up of 88 (range 17-159) months, the patients were scored, using the LENT-SOMA scales, for the following late tissue damage: muscle/soft tissue, peripheral nerves, skin/subcutaneous tissue and vessels. RESULTS: According to the individual SOM parameters of the LENT-SOMA scales, 20 patients (63%) scored grade-3 toxicity on one or more separate items, reflecting severe symptoms with a negative impact on daily activities. Of these patients, 3 (9%) even scored grade-4 toxicity on some of the parameters, denoting irreversible functional damage necessitating major therapeutic intervention. CONCLUSIONS: In evaluating long-term morbidity after a combined treatment procedure for STS of the extremity, using modified LENT-SOMA scores, two-thirds of patients were found to have experienced serious late toxic effects

Radiation-induced cancer after radiotherapy for non-Hodgkin's lymphoma of the head and neck: a retrospective study

<p>Abstract</p> <p>Background</p> <p>survivors of non-Hodgkin's lymphoma (NHL) are well known to be at an increased risk of second malignancies. In this study, we evaluated the incidence and clinical features of head and neck cancer (HNC) occurring after radiotherapy (RT) for NHL.</p> <p>Materials and methods</p> <p>We investigated the clinical records of 322 patients who had received RT for early-stage NHL of the head and neck at our institute between 1952 and 2000.</p> <p>Results</p> <p>There were 4 patients with a second HNC developing in the irradiated field, consisting of 2 patients with gum cancer, 1 case with tongue cancer and 1 case with maxillary sinus cancer. The pathological diagnosis in all the 4 patients was squamous cell carcinoma (SCC). Two of the patients (one with gum cancer and one with maxillary sinus cancer) died of the second HNC, while the remaining 2 patients are still living at the time of writing after therapy for the second HNC, with neither recurrence of the second tumor nor relapse of the primary tumor. The ratio of the observed to the expected number (O/E ratio) of a second HNC was calculated to be 12.7 (95%CI, 4.07–35.0), and the absolute excess risk (AER) per 10,000 person-years was 13.3. The median interval between the RT and the diagnosis of the second HNC was 17.0 years (range, 8.7 to 22.7 years).</p> <p>Conlusion</p> <p>The risk of HNC significantly increased after RT for early-stage NHL. These results suggest that second HNC can be regarded as one of the late complications of RT for NHL of the head and neck.</p

Increased risk of malignancies in a population-based study of 818 soft-tissue sarcoma patients

Soft-tissue sarcomas (STS) have been associated with various rare cancer syndromes and occur at increased frequencies in survivors of childhood cancer. Also adult patients with STS have been suggested to be at an increased risk of additional malignancies. After exclusion of syndrome-associated and radiation-induced sarcomas, we studied multiple primary malignancies in a population-based cohort of 818 patients with primary STS of the extremities and the trunk wall. In total, 203 other malignancies developed in 164 (20%) patients median 10 (0–32) years before and median 4 (0–35) years after the sarcoma diagnosis. Standardised morbidity ratios (SMRs) were determined for primary malignancies following a STS. Hereby individuals who had developed a STS were identified to be at increased risk of second primary malignancies (SMR for all malignant tumours=1.3; 95% CI=1.0–1.5; P=0.02) with STS being the only specific tumour type that occurred at an increased risk (SMR=17.6; 95% CI=8.1–33.5; P<0.001). Hence, this population-based series demonstrates a high frequency of second primary tumours among STS patients and indicates a particularly increased risk of developing a new STS

Radiotherapy for Soft Tissue Sarcomas after Isolated Limb Perfusion and Surgical Resection: Essential for Local Control in All Patients?

Background: Standard treatment for localized soft tissue sarcoma (STS) is resection plus adjuvant radiotherapy (RTx). In approximately 10% of cases, resection would cause severe loss of function or even require amputation because of the extent of disease. Isolated limb perfusion (ILP) with tumor necrosis factor alpha (TNF-α) and melphalan can achieve regression of the tumor, facilitating limb-saving resection. RTx improves local control but may lead to increased morbidity. Methods: In our database of over 500 ILPs, 122 patients with unifocal STS were treated by ILP followed by limb-sparing surgery. All included patients were candidates for amputation. Results: Surgery resulted in 69 R0 resections (57%), and in 53 specimens (43%) resection margins contained microscopic evidence of tumor (R1). Histopathological examination revealed >50% ILP-induced tumor necrosis in 59 cases (48%). RTx was administered in 73 patients (60%). Local recurrence rate was 21% after median follow-up of 31 months (2-182 months). Recurrence was significantly less in patients with >50% ILP-induced necrosis versus ≤50% necrosis (7% vs. 33%, P = 0.001). A similar significant correlation was observed for R0 versus R1 resections (15% vs. 28%, P = 0.04). In 36 patients with R0 resection and >50% necrosis, of whom 21 were spared RTx, no recurrences were observed during follow-up. Conclusions: In patients with locally advanced primary STS, treated with ILP followed by R0 resection, and with >50% ILP-induced necrosis in the resected specimen, RTx is of no further benefit