Addition Of Combination Chemotherapy Research Articles

Splenic Diffuse Red Pulp Small B-Cell Lymphoma Descriptors and Clinicopathologic Determinants of Clinical Outcomes: Analysis of a Pooled Database

Introduction: Splenic Diffuse Red Pulp Small B-Cell Lymphoma (SDRPL) is a rare clinical entity representing <1% of B-Cell Lymphomas. Previously identified as a variant of SMZL, the WHO has recognized it as a provisional entity since its 2008 classification updates. The diagnosis can be challenging as it shares multiple clinical and laboratory features with Splenic Marginal Zone Lymphoma (SMZL), Hairy Cell Leukemia (HCL) and HCL variant (HCL-v). It is characterized by diffuse involvement of the splenic red pulp by small monomorphic B-cells. Due to our limited understanding of this disease, we conducted this pooled database analysis of all cases of SDRPL to delineate key clinicopathological characteristics, prognostic indicators and treatment modalities that affect outcomes in this rare lymphoma subtype. Methods: In order to study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 80 cases. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall (OS) and disease-free survival (DFS) survival. Results: A total of 80 patients with confirmed SDRPL were identified. The median age was 66.5 years, with a peak incidence between 69 and 70. There was a male preponderance with M:F ratio of 1.7. Splenomegaly, hepatomegaly (HM), lymphadenopathy (LN), constitutional symptoms (CS), ECOG0-1, and bone marrow (BM) involvement were present in 91%, 33%, 21%, 44%, 95%, and 95%, respectively. The median splenic weight was 2450g. While splenic red pulp was solely involved in 69% of the cases, 31% had mixed red and white pulp involvement. Three patients had active HBV, one had EBV, 4 had skin involvement, and 1 transformed into B-PLL. SDRPL Immunophenotype consisted of: TRAP(37%), Annexin A1(5%), CD5(14%), CD11c(63%), CD19(97%), CD20&22(100%), CD25(11%), CD27(60%), CD79(100%), CD103(26%), Bcl2(80%), CyclinD1(10%). CyclinD3(55%), and BRAF(16%). The median OS and DFS of the whole group were not reached (mean 138 mo) and 86mo, respectively. Age > 60 adversely impacted DFS (84mo vs. NR, p=0.03). The same trend was noted for age and OS. Compared to no treatment, splenectomy alone and the addition of combination chemotherapy were superior, with a median DFS of 36, 105, and 100 months respectively (p=0.06). HM, BM involvement, WBC>20K, absolute lymphocyte count>5K, and platelets<100K tended to adversely impact DFS, while only BM involvement and platelets<100K tended to impact OS adversely. CD25+ status was detrimental to DFS (36 vs. 105mo, p=0.049) whereas CD103+ status was advantageous to DFS (NR vs. 42mo, p=0.06). When chemotherapy was used, purine analogues tended to have better DFS and OS (76 vs. 26mo, p=0.09) compared to CHOP-like regimens. Neither DFS nor OS was impacted by sex, CS, LN, splenic weight, or splenic white pulp involvement. Conclusions: This study presents an updated clinicopathologic data from a pooled cohort of patients with SDRPL. It identifies the clinical, immunohistochemical, and treatment modalities that are major determinants of DFS and OS in this rare and distinct B-cell lymphoma entity.

Outcomes of surgery and/or combination chemotherapy for extraskeletal osteosarcoma: a single-center retrospective study from China

Extraskeletal osteosarcoma (ESOS) is an extremely rare malignancy with poor prognosis, accounting for 2–4% of all osteogenic sarcomas. The purpose of this study was to examine the oncological outcomes of this disease related to surgical treatment and/or combined adjuvant therapies and to analyze the associated prognostic factors in ESOS. From January 1990 to June 2016, 22 patients with primary ESOS were analyzed in this retrospective study. Overall survival (OS) and progression-free survival (PFS) rates were calculated by Kaplan-Meier methods and compared with log-rank test. 22 patients were diagnosed with ESOS, 19 showed localized diseases and 3 presented with metastatic lesions. The median age at diagnosis was 55.5 years. Surgery resection was performed for all patients, 18 of whom received adjuvant chemotherapy. The median follow-up time was 48.5 months. There were 10 cases of recurrence and 9 patients developed new metastases. The 5-year OS rate for all patients was 58%. For localized cohort, the 5-year OS rate was 62%, and the 3-year PFS rate was 31% with a median PFS of 16 months. Univariate analysis of related prognosis factors showed that larger size of tumor (>5.5 cm) and higher histologic grade emerged as significant factors associated with worse OS. The addition of combination chemotherapy has no effect found on OS or PFS in this study. In summary, for patients who presented with ESOS, larger tumor size and higher histologic grade indicate a lower OS rate. The combination chemotherapy does not improve the OS or PFS.

Adjuvant chemoradiotherapy combined with cisplatin, 5-fluorouracil and folinic acid for locally advanced gastric cancer

Abstract Aim This study retrospectively assessed the efficacy and tolerability of combination chemotherapy with cisplatin, infusional 5-fluorouracil and folinic acid given every two weeks and subsequent chemoradiotherapy with continuous infusions of 5-fluorouracil, in gastric cancer following curative resection. Methods Between August 2007 and January 2014, 58 patients received adjuvant cisplatin 50 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil 400 mg/m2 IV bolus and 5-fluorouracil 2400 mg/m2 as 48-h continuous infusion, every 14 days for gastric adenocarcinoma. After the first 2 cycles of chemotherapy, adjuvant radiation therapy was administered concurrently with the continuous infusion of 5-fluorouracil. Following the completion of radiation therapy, patients received another 4 cycles of combination chemotherapy. Results A total of 58 patients were included in this study and out of these, 41 patients were male and the median age was 53.5 years. 81% of the patients (n = 47) could complete 6 courses of planned chemotherapy. The median follow-up time was 31.4 (9.33–88.77) months, the median disease free survival (DFS) was 26.43 (95% CI: 49.38–69.95) months. The median overall survival (OS) was 28.53 (95% CI: 49.46–69.55) months. The estimated 3-year DFS and OS rates were 58.75% and 64.04% respectively. Common grade 3 and 4 side effects were weakness (18.9%), nausea and vomiting (12%), diarrhea (10.3%) and neutropenia (10.3%). Conclusion The addition of combination chemotherapy with cisplatin, infusional 5-fluorouracil and folinic acid before and after chemoradiotherapy was found to be safe and effective in patients with operated gastric cancer.

Combined chemotherapy and radiation versus radiation alone in the management of localized angiocentric lymphoma of the head and neck

Background and purpose: To clarify the clinical benefit derived from the combined modality therapy (CMT) comprised of chemotherapy and involved-field radiotherapy (XRT) for stage I and II angiocentric lymphomas of the head and neck. Material and methods: Of 143 patients with angiocentric lymphoma of the head and neck treated at the Yonsei Cancer Center between 1976 and 1995, 104 patients (XRT group) received involved-field XRT alone with a median dose of 50.4 Gy (range: 20–70 Gy), while 39 patients (CMT group) received a median three cycles (range: 1–6 cycles) of chemotherapy before starting involved-field XRT. The response rate, patterns of failure, complications, and survival data of the XRT group were compared with those of the CMT group. Results: Despite a higher response rate, local failure was the most common pattern of failure in patients of the both groups. The patterns of failure, including the systemic relapse rate were not influenced by the addition of combination chemotherapy. Although both modalities were well tolerated by the majority of patients, aberrant immunologic disorders or medical illnesses, such as a hemophagocytic syndrome, sepsis, intractable hemorrhage, or the evolution of second primary malignancies were more frequently observed in patients of the CMT group. The prognosis of patients in the XRT group was relatively poor, with a 5-year overall actuarial survival rate of 38% and disease-free survival rate of 32%, respectively. However, their clinical outcome was not altered by the addition of systemic chemotherapy. Achieving complete remission was the most important prognostic factor on univariate and multivariate analyses, but treatment modality was not found to be a prognostic variable influencing survival. Conclusions: Involved-field XRT alone for angiocentric lymphoma of the head and neck was insufficient to achieve an improved survival rate, but the combination of chemotherapy and involved-field XRT failed to demonstrate any therapeutic advantage over involved-field XRT alone.

Combined chemotherapy and radiation versus radiation alone in the management of localized angiocentric lymphoma of the head and neck

Abstract Background and purpose : To clarify the clinical benefit derived from the combined modality therapy (CMT) comprised of chemotherapy and involved-field radiotherapy (XRT) for stage I and II angiocentric lymphomas of the head and neck. Material and methods : Of 143 patients with angiocentric lymphoma of the head and neck treated at the Yonsei Cancer Center between 1976 and 1995, 104 patients (XRT group) received involved-field XRT alone with a median dose of 50.4 Gy (range: 20–70 Gy), while 39 patients (CMT group) received a median three cycles (range: 1–6 cycles) of chemotherapy before starting involved-field XRT. The response rate, patterns of failure, complications, and survival data of the XRT group were compared with those of the CMT group. Results : Despite a higher response rate, local failure was the most common pattern of failure in patients of the both groups. The patterns of failure, including the systemic relapse rate were not influenced by the addition of combination chemotherapy. Although both modalities were well tolerated by the majority of patients, aberrant immunologic disorders or medical illnesses, such as a hemophagocytic syndrome, sepsis, intractable hemorrhage, or the evolution of second primary malignancies were more frequently observed in patients of the CMT group. The prognosis of patients in the XRT group was relatively poor, with a 5-year overall actuarial survival rate of 38% and disease-free survival rate of 32%, respectively. However, their clinical outcome was not altered by the addition of systemic chemotherapy. Achieving complete remission was the most important prognostic factor on univariate and multivariate analyses, but treatment modality was not found to be a prognostic variable influencing survival. Conclusions : Involved-field XRT alone for angiocentric lymphoma of the head and neck was insufficient to achieve an improved survival rate, but the combination of chemotherapy and involved-field XRT failed to demonstrate any therapeutic advantage over involved-field XRT alone.

Systemic therapy for breast cancer.

Currently available information suggests that the optimal duration of adjuvant therapy for breast cancer patients with no involved axillary nodes is 5 years, though controversy about this recommendation persists. In postmenopausal patients, disease-free survival appears to be improved by the addition of combination chemotherapy to tamoxifen. Recently reported studies indicate that there is no benefit to dose escalation of cyclophosphamide in adjuvant therapy and that the risk of secondary leukemia may be increased. The combination of paclitaxel and doxorubicin has been reported in single-institution studies to produce high response rates but may also be cardiotoxic. Recent reports indicate that a pharmacokinetic interaction between these two drugs may cause these clinical findings. New agents that may be of utility in the management of advanced or primary breast cancer include novel hormonal agents, notably the aromatase inhibitors, and the bisphosphonates.

Three-dimensional conformal radiotherapy in bronchogenic carcinoma: considerations for implementation

Lung cancer continues to be a major health problem worldwide. In spite of significant technological and scientific medical progress, the final outcome of this disease is still dismal. Except for a small percentage of patients with early stage who undergo complete surgical resection, local control continues to be disappointingly low. In a recent report by Arriagada et al. (Arriagada R, Le Chevalier T, Quoix E, Rufie P, de Cremoux H, Douillard J-Y, Tarayre M, Pignon, J-P, LaPlanche, A. Effect of chemotherapy on locally advanced non-small cell lung carcinoma: a randomized study of 353 patients. Int J Radiat Oncol Biol Phys 1991; 20: 1183–1190), biopsy proven local control by RT alone was only 17%. This team also found that the addition of combination chemotherapy, although it has decreased distant metastasis, has not had any impact on local control. There are some indications in the literature to suggest that higher doses of radiation to the target volume (tumor) may result in improved local control in inoperable non-small cell lung cancer. This temptation for increasing dose to target volume, however, should not result in inappropriate normal tissue side-effects and complications. Three-dimensional (3D) conformal radiation therapy has shown a significant potential for improving radiation treatment planning in several sites, both for tumor coverage and sparing normal tissue. Using this technology, progress in uncomplicated locoregional control of lung cancer may become a reality. The following is a review of literature and analysis of the currently available information on this subject.

Management of locally recurrent breast cancer

Locoregional recurrences occur commonly in women with breast cancer and often have grave prognostic implications. Major controversies exist concerning the prophylaxis, implications, and treatment of such relapses and are the focus of this review. The relevant medical literature was reviewed and analyzed. Locoregional recurrences may be prevented by postoperative radiation therapy; however, this has little impact on survival. Postoperative systemic therapy prevents locoregional relapse, but less efficiently than radiation therapy. When these modalities are combined, radiation therapy often is delayed until after several cycles of chemotherapy. Optimal sequencing remains controversial. Most patients with locoregional relapses have an exceedingly poor outlook. Radiation therapy provides excellent local control; however, the addition of combination chemotherapy should be considered for patients with defined poor prognostic features. The clinical impact of recurrence in the breast after breast-conserving primary treatment now is emerging. Such local relapses do not have the dreaded prognostic implications of locoregional relapse after mastectomy, but are a marker for an increased risk of dissemination. Standard therapy in this setting remains mastectomy. Additional breast-conserving surgery may be considered in the context of clinical trials for patients with certain favorable features. Conversely, some local relapses after breast-conserving surgery have a poorer prognosis, and the addition of adjuvant systemic therapy should be considered in addition to mastectomy. The heterogenous nature of locoregional relapses has made it difficult to conduct prospective randomized clinical trials. However, many retrospective data exist, making it possible to recommend rational treatment approaches for these patients.

Thyroid lymphomas stages IE and IIE: Comparative result, for radiotherapy only, combination chemotherapy only, and multimodality treatment

This study was undertaken to ascertain the influence of both more precise staging and more intensive treatment on results in 38 patients with Stage IE and IIE lymphomas of the thyroid. These patients were admitted between 1947 and 1984. Using the modified Rappaport system, the disease was classified as diffuse large cell in 32 patients. The initial investigation included lymphangiography in 25 patients, five of which had a staging laparotomy. The assigned stages were IEA-11, IEB-1, and IIEA-26. Treatment consisted of definitive radiotherapy alone in 15; combination chemotherapy and radiotherapy in 14; and chemotherapy alone in 6 patients. The remaining three patients were treated with surgery alone. In general, combination chemotherapy consisted of cyclophosphamide, Adriamycin, vincristine, and prednisone, with or without bleomycin (CHOP ± Bleo). The overall 5-year survival and disease-free survival were 72 and 64%, respectively. For patients treated with radiotherapy only, results depended on stage. For Stage IE, the survival and disease-free survival were 100 and 83%, respectively. The corresponding Stage HE results were 88 and 75%. Within this group, results were better for a subset of patients where disease did not involve the mediastinum. Survival and disease-free survival for combined modality treatment were both 77% (10 of these 17 patients had Stage HE disease). Survival and disease-free survival for combination chemotherapy were 53 and 30% (all had Stage HE disease). In conclusion, radiotherapy alone is excellent treatment for disease limited to the thyroid with or without cervical adenopathy. Results for patients with mediastinal extensions was unsatisfactory and the addition of combination chemotherapy is indicated.

Incidence of hypothyroidism following multimodality treatment for advanced squamous cell cancer of the head and neck.

The incidence of chemical hypothyroidism, as manifested by elevated thyroid stimulating hormone (TSH) levels, has been estimated to be as high as 25% after radiation therapy and 45% after radiation therapy and surgery to the neck for treatment of nodal metastases from squamous carcinoma of the head and neck. We prospectively evaluated 43 previously untreated patients seen in the Dana Farber Cancer Institute Interdisciplinary Head and Neck Service who were treated with aggressive combination chemotherapy in addition to standard surgery and/or radiotherapy. All patients were serially monitored for serum TSH, serum T4, and clinical evidence of hypothyroidism. Following cis-platinum, bleomycin, and methotrexate chemotherapy and subsequent surgery and/or radiotherapy, decreased thyroid reserve appeared in 37% of patients at a median follow-up of 9 months. Thirty percent of patients receiving radiotherapy alone and 43% of patients receiving surgery and radiotherapy developed elevated TSH levels. Only one patient developed clinical symptoms. Other patients were asymptomatic despite persistently elevated TSH levels. Abnormalities appeared within the first 4 months after completion of all therapy and were slowly progressive. The addition of combination chemotherapy does not appear to increase the incidence or severity of thyroid dysfunction following radiation therapy and surgery to the neck. In view of the extended survival seen in patients treated with interdisciplinary regimens, we recommend that all patients receiving irradiation to the neck--particularly those patients having neck dissections or total laryngectomies--have routine thyroid function studies performed following the cessation of treatment.

Stages IIB and IIIB Hodgkin's disease.Results of combined modality treatment

Between April 1969, and December 1974, 23 IIB and 26 IIIB surgically staged patients with Hodgkin's disease were treated at the Joint Center for Radiation Therapy. Stage IIB patients received either mantle and para-aortic-splenic pedicle, or total modal irradiation (TNI) alone or with the addition of combination chemotherapy. Relapse-free survival is 83% and overall survival 88%. Eleven patients received combination chemotherapy in addition to mantle and para-aortic irradiation, and both the relapse-free and overall survival are 100%. Of the stage IIIB patients, seven received TNI alone with four relapses, and 19 were treated with TNI and MOPP with two relapses. These relapse rates are significantly different (p less than 0.05). The relapse-free and overall survival for all stage IIIB patients is 66% and 84% respectively. These data imply that irradiation alone is not adequate treatment for stage IIIB Hodgkin's disease, and that with the addition of combination chemotherapy both the disease-free and overall survival is similar to that of early stage Hodgkin's disease without systemic symptoms. The ideal management of stage IIB Hodgkin's disease is less certain; it is our plan to study the efficacy of combined modality treatment.