Serra Kamer

Primary Mucosa-Associated Lymphoid Tissue Lymphoma of the Salivary Glands: A Multicenter Rare Cancer Network Study

PURPOSE Involvement of salivary glands with mucosa-associated lymphoid tissue (MALT) lymphoma is rare. This retrospective study was performed to assess the clinical profile, treatment outcome, and prognostic factors of MALT lymphoma of the salivary glands. METHODS AND MATERIALS Thirteen member centers of the Rare Cancer Network from 10 countries participated, providing data on 63 patients. The median age was 58 years; 47 patients were female and 16 were male. The parotid glands were involved in 49 cases, submandibular in 15, and minor glands in 3. Multiple glands were involved in 9 patients. Staging was as follows: IE in 34, IIE in 12, IIIE in 2, and IV in 15 patients. RESULTS Surgery (S) alone was performed in 9, radiotherapy (RT) alone in 8, and chemotherapy (CT) alone in 4 patients. Forty-one patients received combined modality treatment (S + RT in 23, S + CT in 8, RT + CT in 4, and all three modalities in 6 patients). No active treatment was given in one case. After initial treatment there was no tumor in 57 patients and residual tumor in 5. Tumor progression was observed in 23 (36.5%) (local in 1, other salivary glands in 10, lymph nodes in 11, and elsewhere in 6). Five patients died of disease progression and the other 5 of other causes. The 5-year disease-free survival, disease-specific survival, and overall survival were 54.4%, 93.2%, and 81.7%, respectively. Factors influencing disease-free survival were use of RT, stage, and residual tumor (p < 0.01). Factors influencing disease-specific survival were stage, recurrence, and residual tumor (p < 0.01). CONCLUSIONS To our knowledge, this report represents the largest series of MALT lymphomas of the salivary glands published to date. This disease may involve all salivary glands either initially or subsequently in 30% of patients. Recurrences may occur in up to 35% of patients at 5 years; however, survival is not affected. Radiotherapy is the only treatment modality that improves disease-free survival.

Differential radiation sensitization of human cervical cancer cell lines by the proteasome inhibitor velcade (bortezomib, PS-341)

Purpose/objective(s)Cervical cancer is one of the deadliest cancers in women with a death toll of 230,000 worldwide each year, nearly 80% in developing countries. Radiotherapy (RT) is a major treatment modality for advanced cervical cancer but the local relapse rate is 30–44% in patients treated with RT alone and 19–25% in patients treated with concurrent chemoradiotherapy. Previous studies have shown that the transcription factor NF-κB is constitutively expressed in human cervical squamous cell carcinomas. NF-κB activation also contributes to the resistance of cervical cancer cells to apoptosis induced by chemotherapeutic agents and radiation. Therefore, inhibition of NF-κB in tumor cells may render them more sensitive to chemo/radiation therapies. The objective of this study is to investigate the potential of radiosensitization of NF-κB inhibition by Velcade in human cervical cancer cell lines.Materials and methods We used the human cervical cancer cell lines HeLa and SiHa. Both are highly radioresistant and chemoresistant as compared to other cervical cancer cell lines. These cells had been treated with Velcade before they were irradiated with different doses of ionizing radiation. MTT metabolic assays and clonogenic cell survival assays were performed to evaluate the effects of Velcade on radiation resistance.ResultsInhibition of NF-κB by Velcade alone decreased metabolic potential (MTT) and clonogenic survival in SiHa, but not in HeLa cells. Furthermore, pre-treatment of SiHa, but not HeLa cells with Velcade enhanced radiation sensitivity.ConclusionsInhibition of NF-κB by the proteasome inhibitor Velcade enhances radiosensitivity of certain human cervical carcinoma cancer cells in vitro. These results raise the possibility that inhibition of NF-κB will result in radiosensitization only in those tumor cells which are more dependent on NF-κB for their metabolism and survival, however, the radiosensitivity of “NF-κB independent” cells are not likely influenced by it.

Does the prognosis of nasopharyngeal cancer differ among endemic and non-endemic regions?

Abstract Conclusion: The survival rates and prognostic factors for nasopharyngeal cancer (NPC) were found to be similar to the published series from endemic regions. Objectives: The purpose of this retrospective study was to evaluate treatment outcome and prognostic factors of NPC patients treated with radiotherapy or chemoradiotherapy in a non-endemic region. Methods: We analyzed clinical characteristics, treatment outcome, and prognostic factors of NPC patients in a non-endemic region, and compared our institutions results with the published literature including a similar patient population from endemic and non-endemic regions. Among 248 NPC patients, 71 (28.6%) were female and 177 (71.4%) were male with a median age of 48 years. Results: Within a median 59 months (range 22–178) of follow-up, local recurrence developed in 22 (8.9%), regional recurrence in 2 (0.8%), locoregional recurrence in 5 (2%), distant metastases in 21 (8.5%), and both locoregional recurrence and distant metastases in 8 (3.2%) patients. Five-year locoregional control (LRC), disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS) rates were 83.7%, 73%, 78.5%, and 71.1%, respectively. In multivariate analysis for LRC, cranial nerve involvement (CNI) (p = 0.009) and tumor response (p = 0.004); for DFS, age (p = 0.003), CNI (p = 0.02), AJCC T classification (p = 0.05), and tumor response (p = 0.01); for DSS, age (p = 0.003), CNI (p = 0.04), AJCC T classification (p = 0.04), and tumor response (p = 0.01); for OS, age (p < 0.001), AJCC T classification (p = 0.005), and tumor response (p < 0.001) were significant prognostic factors.

Acquired activated protein C resistance in sarcoma patients.

Acquired activated protein C resistance (aAPCR) is seen more frequently in solid and hematological cancer patients. We aimed to investigate the presence of aAPCR and the frequency of clinically detectable thrombosis in sarcoma patients. Normalized activated protein C sensitivity ratio (nAPCSR), factor V Leiden (FVL) mutation, factor V (FV) levels and factor VIII (FVIII) levels were prospectively measured in 52 patients and in 52 healthy controls. Clinically detectable thrombosis was present in one patient (1.92%). Compared with healthy controls (106%), the sarcoma patients had significantly lower values of the nAPCSR at pre (87.25%) and post (94.35%) treatment period (P < 0.0001). aAPCR was found as 4.2, 13 and 0%, respectively. The post-treatment FV levels (178.1 U/dl) were significantly (P < 0.001) higher than the pretreatment levels (147.5 U/dl). Inverse correlation was found between post-treatment FV levels and nAPCSR values (r = −0.38, P < 0.02). We found out a slightly increased frequency of venous thromboembolism in sarcoma patients. As an original finding which has not been reported previously in the literature, we also found out a decrease in the nAPCSR, persisting even after treatment. Thirdly, we found out that the significantly higher rate of aAPCR at the time of diagnosis totally disappeared after treatment.

Daily subcutaneous amifostine administration during irradiation of pediatric head and neck cancers

Five pediatric patients with head and neck cancers were treated with radiotherapy. Subcutaneous injections of 200 mg flat dose amifostine were given 30 min prior to radiation fractions. A total of 129 amifostine injections were done. Grade 3 nausea occurred three times and emesis only once. Hypotension, hypocalcemia, or allergic reactions following injections were not recorded. No grade 3 or 4 mucosal or skin reactions occurred. After 16 months, all patients were alive and disease‐free. There were no grade 3 or 4 side effects of radiotherapy on follow‐up. Further studies with more patients are required to determine the role of amifostine in pediatric radiation oncology, but these data should contribute to the clinical spectrum of amifostine use in pediatric oncology. Pediatr Blood Cancer 2007;48:579–581.

Successful Treatment With Total Skin Electron Beam Therapy in a Child With Isolated Cutaneous Relapsed AML.

A 9-year-old girl diagnosed with acute myeloblastic leukemia M4 developed isolated cutaneous relapse. She was given chemotherapy including idarubicin, fludarabine, and cytarabine. Although she developed very severe pancytopenia, increase in the number and size of the lesions was seen. Total skin electron beam therapy was applied to the skin lesions for a total of 18 Gy. All lesions responded to total skin electron beam therapy, some of them completely disappeared. After resolution of the skin findings, she underwent bone marrow transplantation from her matched brother. Twenty-six months after hematopoietic stem cell transplantation she is alive without any event.

Treatment outcome and prognostic factors for adult patients with medulloblastoma: The Rare Cancer Network (RCN) experience

BACKGROUND AND PURPOSE The optimal treatment for adults with newly diagnosed medulloblastoma (MB) has not been defined. We report a large series of cases from the Rare Cancer Network. MATERIAL AND METHODS Thirteen institutions enrolled 206 MB patients who underwent postoperative radiotherapy (RT) between 1976 and 2014. Log-rank univariate and Cox-modeled multivariate analyses were used to analyze data collected. RESULTS Median patient age was 29 years; follow-up was 31 months. All patients had the tumor resected; surgery was complete in 140 (68%) patients. Postoperative RT was given in 202 (98%) patients, and 94% received craniospinal irradiation (CSI) and, usually, a posterior fossa boost. Ninety-eight (48%) patients had chemotherapy, mostly cisplatin and vincristine-based. The 10-year local control, overall survival, and disease-free survival rates were 46%, 51%, and 38%, respectively. In multivariate analyses, Karnofsky Performance Status (KPS) ≥80 and CSI were significant for disease-free and overall survival (P ≤ .04 for all); receiving chemotherapy and KPS ≥80 correlated with better local-control rates. CONCLUSIONS Patients with high KPS who received CSI had better rates of disease-free and overall survival. Chemotherapy was associated with better local control. These results may serve as a benchmark for future studies designed to improve outcomes for adults with medulloblastoma.

Adult Onset Langerhans Cell Histiocytosis: A Single Center Experience

Non-Hodgkin Lymphoma

The role of radiotherapy in local control of nonextremity Ewing sarcomas.

Purpose To evaluate the results of radiotherapy and the prognostic factors affecting local control in nonextremity Ewing sarcomas. Methods Between 1995 and 2011, 44 patients with nonextremity Ewing sarcomas were treated with radiotherapy. Tumor localizations were pelvis in 23, spine in 13, thoracic region in 5, and cranium in 3 patients. Tumor size was ≥8 cm in 56.8% of patients. Distant metastases were present in 19 of the patients at the time of diagnosis (43.1%). All patients were treated with 12 weeks of neoadjuvant chemotherapy followed by surgery and radiotherapy (45-54 Gy) or radiotherapy alone (54-64.8 Gy). Radiotherapy was applied due to microscopic residue (R1) in 5 patients after the operation and macroscopic tumor in 39 patients (macroscopic residue [R2] and nonresectable tumor). Results Median follow-up was 49 months (range 9-195). Local failures developed in 7 patients (15.9%) and local control at 5 years was 81.4%. Local recurrence was detected in 6 patients (6/38) who did not have residual tumor after RT. Progression was detected in 1 patient (1/6) who had residual tumor. All those patients with local failure experienced further distant metastases. Possible prognostic factors such as age (≤17 vs >17), tumor localization, tumor volume (≤8 cm vs >8 cm), and M status at diagnosis (0 vs 1) were not related to local control. Conclusions Radiotherapy, either alone or adjuvant to surgery, provides local control in 80% of nonextremity Ewing sarcomas and plays an important role in treatment.

Mechanisms of Resistance to Radiation

Radiotherapy is a very effective treatment for achieving local tumor control in breast cancer. However, intrinsic tumor cell radioresistance is a significant clinical problem that limits the results of the treatment. Chemotherapeutics that could specifically sensitize tumors to radiation would greatly increase the ability to deliver higher doses while limiting radiation damage to surrounding normal tissue, but efforts to develop clinically useful tumor radiosensitizers have had limited success.