Reduction of the treated volume to involved node radiation therapy as part of combined modality treatment for early stage aggressive non-Hodgkin’s lymphoma

Background and purpose

This retrospective study investigated whether focused involved node radiation therapy (INRT) can safely replace involved field RT (IFRT) in patients with early stage aggressive NHL.

Patients and methods

We included 258 patients with stage I/II aggressive NHL who received combined modality treatment (87%) or primary RT alone (13%). RT consisted of a total dose of 30–40 Gy in 15–20 fractions IFRT or INRT. We compared survival, relapse pattern, radiation-related toxicity and quality of life for both RT techniques.

Results

Type of RT was not related to the outcome in either the uni- or multivariate survival analysis. Relapses developed in 59 of 252 patients (23%) of which 47 (80%) were documented as distant recurrence only. Failure of the INRT technique was noted in one patient. There was no significant difference in acute radiation-related toxicity between RT-groups but IFRT showed a significantly higher incidence of higher grade toxicities. Patients treated with INRT had a significantly better physical functioning and global quality of life compared to the IFRT group.

Conclusions

Given the retrospective nature of this study, no solid conclusions can be drawn. However, in view of the equivalent efficacy and more favorable toxicity profile, the replacement of IFRT by INRT in combination with chemo-(immuno)-therapy looks very attractive for patients with early stage aggressive NHL.     

DIBH技术对纵隔淋巴瘤累及部位放疗靶区与OAR受量影响

目的 探讨深吸气屏气(DIBH)技术对纵隔淋巴瘤放疗靶区和正常组织受量影响。方法 前瞻性采集连续收治的5例Ⅰ、Ⅱ期纵隔淋巴瘤病例。采用受累部位照射和蝴蝶野设野原则,对比DIBH和自由呼吸(FB)扫描时靶区绝对体积变化、重要OAR绝对剂量体积和相对剂量-体积差别。配对t检验差异。结果 5例中位年龄30岁。与FB相比DIBH时靶区绝对体积化疗前GTV缩减29.4 cm³(P=0.006),PTV缩减322 cm³(P=0.005);肺绝对体积平均增大1456 cm³(P=0.001),心脏宽度缩小1.3 cm (P=0.012)。DIBH时心脏和肺D_mean显著降低(心脏为8.5 Gy∶11.6 Gy,P=0.022;肺为7.6 Gy∶11.6 Gy,P=0.000)。比较受一定水平照射的绝对体积时,心脏在高剂量水平V₁₅及以上显著降低(P均<0.05)。DIBH时肺和心脏相对百分比在所有剂量水平(V₅—V₃₅)均显著小于FB (P均<0.05)。结论 纵隔淋巴瘤放疗,DIBH技术能显著缩小PTV,增加肺体积,且显著降低心肺D_mean和V₅—V₃₅水平的相对剂量-体积参数。     

Low-dose and limited-volume radiotherapy alone for primary dural marginal zone lymphoma: treatment approach and review of published data

PURPOSE: Primary dural lymphoma is a rare intracranial lymphoma that almost always has a marginal zone histologic type and immunophenotype and often remains localized and is thus potentially curable with radiotherapy (RT) alone. The unusual location and histologic type of primary dural marginal zone lymphoma (PDMZL) distinguish it from primary central nervous system lymphoma and poses treatment dilemmas of technique, volume, and dose that have not been well addressed. We set out to analyze our recent experience in treating PDMZL and reviewed the limited published data available. METHODS AND MATERIALS: Between 2002 and 2006, we treated 5 patients with localized PDMZL. Of these 5 patients, 3 had unilateral and 2 had bilateral/multifocal involvement, and 3 underwent subtotal tumor resection and 2 biopsy only. Whole brain RT was given before involved-field RT (IFRT) in 4 patients and 1 received IFRT alone. The median whole brain RT, IFRT, and total RT dose was 20, 12, and 30 Gy, respectively. The planning computed tomography scan was always fused with the post-gadolinium magnetic resonance imaging scan to assist in the IFRT volume determination. We also analyzed the published data from 27 additional patients. RESULTS: The median follow-up was 34 months (range, 31-52). All obtained lasting local control. One patient developed a relapse in the soft tissue of the flank and additional systemic progression but no central nervous system recurrence. At last follow-up, no significant treatment-related neurotoxicity was detected. CONCLUSION: The results of our study have demonstrated that a combination of whole brain RT/IFRT or even low-dose IFRT alone provides excellent durable local control of PDMZL. This approach is potentially curative, possibly without significant neurotoxicity. Additional study and longer follow-up are needed to determine the appropriate RT dose and volume parameters for this rare, debilitating, and yet potentially curable lymphoma.     

The Case for Chemotherapy Alone for Limited-Stage Hodgkin's Lymphoma

The Hodgkin''s Disease.6 study is critically examined, and the question of whether or not radiation should be used at all in the treatment of patients with limited-stage Hodgkin''s lymphoma is argued to be more relevant than what type of radiation to use, given the remarkably good outcome with chemotherapy alone.     

Direct comparisons of peripheral T-cell lymphoma with diffuse B-cell lymphoma of comparable histological grades--should peripheral T-cell lymphoma be considered separately?

Peripheral T-cell lymphoma (PTCL) forms a morphologically heterogeneous group of non-Hodgkin's lymphomas (NHL) with distinct immunophenotypes of mature T cells. Progress has been slow in defining specific clinicopathological entities to this particular group of NHL. In order to elucidate the specific characteristics of PTCL, a direct comparison of PTCL with a group of diffuse B-cell lymphomas (DBCL) was performed. Between June 1983 and December 1987, we studied 114 adults with NHL, using a battery of immunophenotyping markers. Adult T-cell leukemia/lymphoma, lymphoblastic lymphoma, mycosis fungoides/Sézary syndrome, follicular lymphoma, well-differentiated lymphocytic lymphoma, and true histiocytic lymphoma were excluded from this study since these are distinct clinicopathologic entities with well-recognized immunophenotypes. Of the remaining 75 patients, 70 who had adequate clinical information were analyzed, and of these, 34 were PTCL and 36 were DBCL. Classified according to the National Cancer Institute (NCI) Working Formulation (WF), 68% of PTCL and 31% of DBCL were high-grade lymphomas. Clinical and laboratory features were similar, except PTCL had a characteristic skin involvement and tended to present in more advanced stages with more constitutional symptoms. Induction chemotherapy was homogeneous in both groups, and complete remission rates were 62% for PTCL and 67% for DBCL. Patients with DBCL had a better overall survival than patients with PTCL, but the survival benefit disappeared after patients were stratified according to intermediate- or high-grade lymphoma. A subgroup of PTCL patients who had received less intensive induction chemotherapy was found to have a very unfavorable outcome. We conclude that (1) PTCL follows the general grading concept proposed in WF classification; (2) within a given intermediate or high grade, PTCL and DBCL respond comparably to treatment; (3) the intensity of induction chemotherapy has a crucial impact on the outcome of PTCL patients; and (4) with a few exceptions, the clinical and laboratory features of PTCL and DBCL are comparable.     

Involved-field, low-dose chemoradiotherapy for early-stage anal carcinoma

PURPOSE: To report the results of patients with early-stage anal cancer treated using a low-dose, reduced-volume, involved-field chemoradiotherapy protocol. METHODS AND MATERIALS: Between June 2000 and June 2006, 21 patients were treated with external beam radiotherapy (30 Gy in 15 fractions within 3 weeks) and concurrent chemotherapy (bolus mitomycin-C 12 mg/m(2) on Day 1 to a maximum of 20 mg followed by infusion 5-fluorouracil 1,000 mg/m(2)/24 h on Days 1-4). Of the 21 patients, 18 underwent small-volume, involved-field radiotherapy and 3 were treated with anteroposterior-posteroanterior parallel-opposed pelvic fields. Of the 21 patients, 17 had had lesions that were excised with close (<1 mm) or involved margins, 1 had had microinvasive disease on biopsy, and 3 had had macroscopic tumor <2 cm in diameter (T1). All were considered to have Stage N0 disease radiologically. RESULTS: After a median follow-up of 42 months, only 1 patient (4.7%) had experienced local recurrence and has remained disease free after local excision. No distant recurrences or deaths occurred. Only 1 patient could not complete treatment (because of Grade 3 gastrointestinal toxicity). Grade 3-4 hematologic toxicity occurred in only 2 patients (9.5%). No significant late toxicity was identified. CONCLUSION: The results of our study have shown that for patients with anal carcinoma who have residual microscopic or very-small-volume disease, a policy of low-dose, reduced-volume, involved-field chemoradiotherapy produces excellent local control and disease-free survival, with low rates of acute and late toxicity.     

Hitting a Moving Target: Successful Management of Diffuse Large B-cell Lymphoma Involving the Mesentery With Volumetric Image-guided Intensity Modulated Radiation Therapy

Introduction

We report successful treatment of mesenteric diffuse large B-cell lymphoma (DLBCL) using localized involved site radiation therapy (ISRT), intensity modulated radiation therapy (IMRT), and daily computed tomography (CT)-image guidance.

Breast conserving therapy after neoadjuvant chemotherapy; data from the Dutch Breast Cancer Audit

IntroductionNAC has led to an increase in breast conserving surgery (BCS) worldwide. This study aims to analyse trends in the use of neoadjuvant chemotherapy (NAC) and the impact on surgical outcomes.MethodsWe reviewed all records of cT1-4N0-3M0 breast cancer patients diagnosed between July 2011 and June 2016 who have been registered in the Dutch National Breast Cancer Audit (NBCA) (N = 57.177). The surgical outcomes of 'BCS after NAC′ were compared with 'primary BCS′, using a multivariable logistic regression model.ResultsBetween 2011 and 2016, the use of NAC increased from 9% to 18% and 'BCS after NAC' (N = 4170) increased from 43% to 57%. We observed an involved invasive margin rate (IMR) of 6,7% and a re-excision rate of 6,6%. As compared to 'primary BCS′, the IMR of 'BCS after NAC′ is higher for cT1 (12,3% versus 8,3%; p < 0.005), equal for cT2 (14% versus 14%; p = 0.046) and lower for cT3 breast cancer (28,3% versus 31%; p < 0.005). Prognostic factors associated with IMR for both 'primary BCS′ as for 'BCS after NAC′ are: lobular invasive breast cancer and a hormone receptor positive receptor status (all p < 0,005).ConclusionThe use of NAC and the incidence of 'BCS after NAC′ increased exponentially in time for all stages of invasive breast cancer in the Netherlands. This nationwide data confirms that 'BCS after NAC′ compared to 'primary BCS′ leads to equal surgical outcomes for cT2 and improved surgical outcomes for cT3 breast cancer. These promising results encourage current developments towards de-escalation of surgical treatment.     

Tumor burden in Hodgkin's lymphoma can be reliably estimated from a few staging parameters

The relative tumor burden (rTB), the tumor burden normalized to body surface area, is of prime clinical and prognostic value in Hodgkin's lymphoma. However, its measurement is rather complicated and a bedside computation cannot be proposed. We investigated the possibility of estimating, instead of measuring, rTB from elementary parameters of the initial staging. The rTB of 507 patients, treated with therapeutic protocols of the Gruppo Italiano Studio Linfomi according to their staging characteristics, was measured through their pre-therapy computed tomographies. The relationships between rTB and staging characteristics were analyzed with simple and multiple regressions both in a training sample (254 patients) for a selection of predictive parameters, and in a test sample (253 patients) for validation of the results. The number of involved sites, bulky mass and the IPI score were the variables best related to rTB. The resulting final equation {estimated rTB=-4.3+8.3xIPI2+22.7x[no. of involved sites (+3 if a bulky mass is present)]} provided the maximal approximation to the measured rTB (R2=0.671). The validity of the equation was confirmed on the test sample and the predictive superiority of the estimated rTB over IPI was still evident in terms of failure-free survival in both groups of patients. The estimated rTB is accurate enough to retain most of the prognostic advantage of the measured rTB over the IPI score. It can be easily calculated, allows a valid approximation of the measured rTB, and can be proposed as a useful tool for clinical research and practice.     

The Case for Combined-Modality Therapy for Limited-Stage Hodgkin's Disease

Results of the Hodgkin''s Disease.6 trial are critically examined in light of the advances in radiation therapy techniques that have occurred since it was initiated. The ultimate findings of the HD.6 trial do not close the case for combined-modality treatment of limited-stage Hodgkin''s disease.     

Toxicities and effects of involved-field irradiation with concurrent cisplatin for unresectable carcinoma of the pancreas

PURPOSE: To evaluate local effects and acute toxicities of involved field irradiation with concurrent cisplatin (CDDP) for unresectable pancreatic carcinoma. MATERIALS AND METHODS: Thirty-three patients with unresectable pancreatic carcinoma were treated with chemoradiotherapy. Sixteen were Stage IVA; 17 were Stage IVB. The total prescribed dose of radiotherapy was 50 Gy/25 fractions or 50.4 Gy/28 fractions, using a three-dimensionally determined involved-field that included only the primary tumor and clinically enlarged lymph nodes. Twelve patients received a daily i.v. infusion of CDDP; 21 patients received a combination of CDDP and 5-fluorouracil either i.v. or through the proper hepatic artery. RESULTS: Twenty-seven (82%) patients completed planned chemoradiotherapy. Nausea was the most frequent complaint. No patient experienced Grade 4 toxicities. More than half achieved pain relief. As for the primary site, only 4 patients (12%) achieved a partial response at 4 weeks; however, 3 additional patients attained >50% tumor reduction thereafter. The most frequent site of disease progression was the liver, and only 3 patients developed local progression alone. No regional lymph nodal progression outside the treatment field was seen. Median survival time and survival at 1 year were 7.1 months and 27%, respectively, for the entire group. Difference in overall survival between patients with and without distant metastases was significant (p = 0.01). CONCLUSIONS: Involved-field irradiation with concurrent daily CDDP was well tolerated without compromising locoregional effects.     

Can patients with early-stage diffuse large B-cell lymphoma be treated without bone marrow biopsy?

BACKGROUND: Data on the incidence of bone marrow (BM) involvement in early-stage diffuse large B-cell lymphoma (DLBCL) are lacking. Although BM biopsy is a safe procedure, it is often poorly tolerated. This analysis aims to assess the incidence of BM involvement and to identify parameters predicting BM involvement in early-stage DLBCL. PATIENTS AND METHODS: One hundred and ninety-two patients with radiological stages 1 and 2 disease were analysed. The data collected were age, sex, presence of B symptoms, white blood cell (WBC) count, platelet count, haemoglobin (Hb), serum lactate dehydrogenase level, serum beta(2)-microglobulin level, presence of extranodal disease, and the presence of bulky disease (defined as >7 cm). RESULTS: Overall incidence of BM involvement was 3.6%. Hb < 10 g/dl (P=0.02), WBC count < 4 x 10(9)/l (P=0.007) and bulky disease (P=0.06) were found to be predictive of BM involvement. Among the 120 patients without any of these three factors, only one patient had BM involvement (0.83%; 95% confidence interval 0.02% to 4.6%). The absence of all three factors gave a negative predictive value of 99.2%. Overall 3-year survival for patients without all three risk factors was 80%. CONCLUSIONS: BM biopsy may be safely omitted in selected patients with early-stage DLBCL.