Combined Modality Therapy For Patients Research Articles

Outcomes with Immunochemotherapy Plus Radiation Versus Immunochemotherapy Alone in Stage I Diffuse Large B-Cell Lymphoma: A Retrospective Study

Introduction Diffuse Large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma with a prognosis highly dependent on the stage of the disease. The mainstay of front-line therapy for limited-stage DLBCL is R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) or R-CHOP-like immunochemotherapy (IC). The impact of combined modality therapy (CMT) with radiation therapy (RT) after IC remains uncertain in the rituximab era. In the pre-rituximab era, studies comparing the efficacy of chemotherapy with or without RT showed heterogenous results. To date, only a few single institutional studies have compared IC versus CMT. The aim of this study is to evaluate the efficacy of standard IC compared to CMT in patients with stage I DLBCL in the rituximab era. Methods Adult patients with stage I DLBCL diagnosed between 2002 to 2015 and seen at Mayo Clinic Rochester were identified. Data were obtained from medical records. All patients were treated with IC (R-CHOP or R-CHOP-like), or IC followed by radiation (CMT). The student's t-test or the Wilcoxon rank-sum test was used to analyze between-group differences, as appropriate. Chi-square or Fisher's exact test was used for categorical variable comparisons. Progression-free survival (PFS) was defined as the time from the date of diagnosis to the date of relapse, death or the date of the last follow-up and was analyzed using the Kaplan-Meier method. Overall survival (OS) was defined as the time from the date of diagnosis to the date of last follow-up or death. Response to treatment was evaluated by treating physicians. Results The study included 123 patients diagnosed with stage I DLBCL with a median follow-up time of 65.9 months for IC arm and 56.2 months for CMT arm. Overall, 78 patients were treated with six cycles of IC, and 45 patients were treated with 2-4 cycles of IC followed by involved-site radiation (2 cycles in 4 patients, 3 cycles in 25 patients, 4 cycles in 16 patients). There were no significant differences in age, sex, or extranodal involvement. In the IC group, 59 patients had cell of origin data available: 44 (56.41%) were GCB subtype and 15 patients (19.23%) were non-GCB subtype. In the CMT group, 21 patients (47%) and 9 patients (20%) had GCB and non-GCB subtypes, respectively. Double-hit lymphoma (defined as rearrangement of MYC together with rearrangement of BCL2 and/or BCL6) was reported in 4 out of 78 patients in the IC arm and 2 out of 45 patients in the CMT arm. There was no significant difference in response rates to frontline treatment between groups. In the IC group, the overall response rate (ORR) was 92% (n=72), and the rate of complete response (CR) was 87% (n=68), partial response (PR) was 5% (N=4), stable disease (SD) was 5% (n=4), and progressive disease (PD) was 5% (n=4). In the CMT group, the ORR was 96% (n=43, all CR); 2 patients achieved SD (4%) and no patients had a PR or PD. With a median follow-up time of 65.9 months for IC arm, 14 patients had died. With a median follow-up of 56.2 months for the CMT arm, 14 patients had died. Median PFS was not reached in the IC group while PFS was more than 10 years in the CMT group (p=0.7851) [Figure 1]. There was no significant OS difference observed in both groups (p=0.2561) [Figure 2]. Conclusion Our study showed no significant difference in OS and PFS between patients with stage I DLBCL treated with IC or CMT. Future research on a larger patient population is needed to evaluate the role of consolidation radiotherapy in early stage DLBCL. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Combined modality therapy for patients with esophageal squamous cell carcinoma: Radiation dose and survival analyses.

We aimed to analyze the radiation dose and compare survival among combined modality therapy using modern radiation techniques for patients with esophageal squamous cell carcinoma (ESCC). This retrospective study included patients with clinically staged T1-4N0-3M0 ESCC from 2014 to 2018. Patients who received combined modality therapies with curative intent were enrolled. The overall survival (OS) rates among combined modality therapy were compared. The clinical variables and impacts of radiation dose on survival were analyzed by the Kaplan-Meier method and Cox regression model. Of the 259 patients, 141 (54.4%) received definitive concurrent chemoradiotherapy (DCCRT); 67 (25.9%) underwent neoadjuvant chemoradiotherapy followed by surgery (NCRT+S); 51 (19.7%) obtained surgery followed by adjuvant chemoradiotherapy (S+ACRT). Two-year OS rates of the DCCRT, NCRT+S and S+ACRT group were 48.9, 61.5 and 51.2%. In the subgroup analysis of DCCRT group, the 2-year OS of patients receiving radiation dose 55-60 Gy was 57.1%. Multivariate analyses showed that clinical stage (p=0.004), DCCRT with 55-60 Gy (p=0.043) and NCRT+S with pathological complete response (pCR) (p=0.014) were significant prognostic factors for better OS. The radiation dose-survival curve demonstrated a highly positive correlation between higher radiation dose and better survival. Our results suggest that NCRT+S can provide a favorable survival for patients with ESCC, especially in patients who achieved pCR. The optimal radiation dose might be 55-60 Gy for patients receiving DCCRT via modern radiation techniques. Further randomized clinical studies are required to confirm the survival benefits between NCRT+S and DCCRT with escalated dose.

The Addition of Chemoradiation to Adjuvant Chemotherapy is Associated With Improved Survival Following Upfront Surgical Resection for Pancreatic Cancer With Nodal Metastases.

BackgroundIt is unclear whether the addition of chemoradiation (CRT) to adjuvant chemotherapy (CT) following upfront resection of pancreatic ductal adenocarcinoma (PDAC) provides any benefit. While some studies have suggested a benefit to combined modality therapy (CMT) (adjuvant CT plus CRT), it is not clear if this benefit was related to increased CT usage in patients who received CMT. We sought to clarify the use of CMT in patients who underwent upfront resection of PDAC.MethodsPatients with non-metastatic PDAC were retrospectively identified from the linked SEER-Medicare database. Those who underwent upfront resection were identified and divided into two cohorts – patients who received adjuvant CT and patients who received adjuvant CMT. Cohorts were compared. Univariate analysis described patient characteristics. Kaplan-Meier and multivariable Cox proportional hazards modeling were used to estimate overall survival (OS).Results3555 patients were identified; 856 (24%) received CT and 573 (16%) received CMT. The median number of CT doses was 11 for both groups. Patients who received CMT were younger, diagnosed in the earlier time frame, and had fewer comorbidities. The median OS was 21 months and 18 months for those treated with CMT and CT (P < .0001), respectively, but when stratified by nodal status, the association with improved OS in the CMT cohort was only observed in node-positive patients. On multivariable analysis, receipt of CMT and removal of >15 lymph nodes decreased the risk of death (P < .05).DiscussionReceipt of CMT following upfront resection for PDAC was associated with improved survival, which was confined to node-positive patients. The role of adjuvant CMT in PDAC with nodal metastases warrants further study.

First-Line Treatment and Survival of Stage I(E) Peripheral T-Cell Lymphoma in the Netherlands; A Nationwide Population-Based Cohort Study

Introduction: Peripheral T-cell lymphomas (PTCL) comprise a heterogenous group of mature T-cell neoplasms with generally an unfavorable prognosis. Presentation of PTCL with stage I(E) disease, according to the Ann Arbor classification, is uncommon. Clinical trials in diffuse large B-cell lymphoma (DLBCL) support the use of an abbreviated treatment with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone combined with radiotherapy (combined modality therapy (CMT)) in case of stage I(E) disease. CMT in stage I(E) PTCL has been adapted in daily practice, but clinical trials are lacking. A recent population-based study conducted in Scandinavia indicated that the outcome in patients with limited stage PTCL is as poor as in patients with extensive disease. However, the outcomes of different treatment modalities were not analyzed.Aim: The aim of this nationwide population-based cohort study is to describe first-line treatment and outcome of patients with stage I(E) PTCL in comparison to advanced stage PTCL.Methods: All newly diagnosed patients ≥ 18 years with stage I(E) PTCL who were diagnosed in 1989-2018 were identified in the Netherlands Cancer Registry (NCR). Survival follow-up was available through February 1, 2021. The PTCL subgroups analyzed included anaplastic large cell lymphoma (ALCL), angioimmunoblastic T-cell lymphoma (AITL), enteropathy associated T-cell lymphoma (EATL) and peripheral T-cell lymphoma NOS (PTCL NOS). Patients were categorized according to treatment regimen, i.e. chemotherapy, chemotherapy followed by autologous stem cell transplantation (ASCT), radiotherapy, CMT, and no/other therapy. Calendar period analyses (1989-1999 and 2000-2018) were conducted to assess trends in primary therapy and overall survival (OS) over time. The calendar periods were defined according to the implementation of CMT in patients with limited stage DLBCL from approximately 2000 onward in the Netherlands. The primary endpoint was OS, defined as all-cause-death post-diagnosis.Results: From 1989 to 2018, 854 patients with a median age of 62 years were diagnosed with stage I(E) PTCL, accounting for 19% of all PTCL diagnoses. In stage I(E), the predominant PTCL subtype was PTCL NOS (40%, n=343). Furthermore, 26% (n=222) of patients were diagnosed with ALCL, 3% (n=28) with AITL, 11% (n=93) with EATL and 20% (n=168) with other histological subtypes. In contrast, for patients with advanced stage disease, 42% was diagnosed with PTCL NOS, 23% with ALCL, 24% with AITL, 6% with EATL and 5% with other histological subtypes .To evaluate treatment and survival outcome in patients with stage I(E) PTCL, patients with ALCL, AITL, PTCL NOS and EATL were included for further analyses (n=686). Patients with ALCL, AITL and PTCL NOS were most commonly treated with CMT (n=164; 28%) or chemotherapy only (n=154; 26%). Only 10 patients (1%) received chemotherapy followed by ASCT. The remaining patients were treated with either radiotherapy only (n=116; 20%) or received other/no therapy (n=149; 25%). More patients were treated with CMT in 2000-2018 as compared to 1989-1999 (36% versus 17%, p<0.01). Patients with EATL were most commonly treated with either chemotherapy only or other/no treatment (both n=45; 48%), while 3 patients (4%) received chemotherapy in combination with ASCT (n=2) or CMT (n=1). In EATL, no differences in treatment strategy were observed over time.Overall, 5-year OS for all stage I(E) PTCL was 52%. There was no significant difference in outcome between the two time periods (53% vs. 52%, p=0.92). EATL had a worse prognosis when compared to ALCL, AITL and PTCL NOS (5-year OS 15% vs. 58%, respectively; p<0.01). Five-year OS was significantly higher for patients with ALCL, AITL and PTCL NOS treated with CMT (71%) as compared to patients treated with either chemotherapy alone or with radiotherapy alone (52%, and 53%, respectively; p<0.01). Independent predictors for poor prognosis were higher age, male gender and EATL subtype whereas CMT was associated with a lower risk of mortality when evaluated for in multivariable analysis.Conclusions: For stage I(E) ALCL, AITL and PTCL NOS, 5-year OS is 58%. This compares favorably to the reported outcomes in advanced stage disease. EATL, even when presenting with limited stage disease, is associated with a very poor prognosis. CMT is associated with superior OS when compared to either chemotherapy or radiotherapy alone. DisclosuresVan Der Poel: Roche, Janssen, Abbvie: Honoraria. Kersten: Kite/Gilead: Consultancy, Honoraria, Research Funding; BMS/Celgene: Consultancy; Miltenyi Biotech: Consultancy; Novartis: Consultancy, Honoraria; Roche: Honoraria; Takeda: Consultancy. Mutsaers: BMS: Consultancy; AstraZeneca: Research Funding. Woei-a-Jin: University Hospitals Leuven, Belgium: Current Employment; Recordati: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Kyowa Kirin: Research Funding.

The association of age with acute toxicities in NRG oncology combined modality lower GI cancer trials

PurposeExpected toxicity from chemoradiation (CRT) is an important factor in treatment decisions but is poorly understood in older adults with lower gastrointestinal (GI) malignancies. Our objective was to compare acute adverse events (AAEs) of older and younger adults with lower GI malignancies treated on NRG studies. MethodsData from 6 NRG trials, testing combined modality therapy in patients with anal or rectal cancer, were used to test the hypothesis that older age was associated with increased AAEs. AAEs and compliance with protocol-directed therapy were compared between patients aged ≥70 and < 70. Categorical variables were compared across age groups using the chi-square test. The association of age on AAEs was evaluated using a covariate-adjusted logistic regression model, with odds ratio (OR) reported. To adjust for multiple comparisons, a p-value <0.01 was considered statistically significant. ResultsThere were 2525 patients, including 380 patients ≥70 years old (15%) evaluable. Older patients were more likely to have worse baseline performance status (PS 1 or 2) (23% vs. 16%, p = 0.001), but otherwise baseline characteristics were similar. Older patients were less likely to complete their chemotherapy (78% vs. 87%, p < 0.001), but had similar RT duration. On univariate analysis, older patients were more likely to experience grade ≥ 3 GI AAEs (36% vs. 23%, p < 0.001), and less likely to experience grade ≥ 3 skin AAEs (8% vs. 14%, p = 0.002). On multivariable analysis, older age was associated with grade ≥ 3 GI AAE (OR 1.93, 95% CI: 1.52, 2.47, p < 0.001) after adjusting for sex, race, PS, and disease site. ConclusionsOlder patients with lower GI cancers who underwent CRT were less likely to complete chemotherapy and had higher rates of grade 3+ GI AAEs. These results can be used to counsel older adults prior to treatment and manage expected toxicities throughout pelvic CRT.

Long-term outcomes after bladder-preserving combined-modality therapy for patients with muscle-invasive bladder cancer.

398 Background: Transurethral resection of bladder tumor (TURBT), chemotherapy (CT), and radiation therapy (RT) is an established treatment paradigm for muscle-invasive bladder cancer (MIBC). Herein we report long-term outcomes for MIBC patients treated with combined-modality therapy (CMT). Methods: We analyzed 465 patients with MIBC (cT2-T4a) treated on successive protocols at a single center between 1986 and 2012. Patients underwent TURBT followed by concurrent cisplatin-based chemoradiation (CRT). A subset of patients received neoadjuvant CT. Repeat cystoscopy was performed after 40 Gy. Patients with a complete response (CR) received consolidation CRT to 64-65 Gy, while those with less than a CR or invasive recurrence were recommended to undergo salvage RC. Overall survival (OS) and disease-specific survival (DSS) were evaluated using Kaplan-Meier method and Cox proportional hazards regression. Results: Median follow-up was 4.8 years for all patients and 7.5 years for surviving patients. CR to induction CRT was achieved in 76% patients; 84% of patients with a complete TURBT achieved a CR vs. 59% with an incomplete TURBT, p&lt; 0.001. When evaluated in four-year intervals, the CR rate improved from 64% in 1986-1990 to 96% in 2010-2012. Salvage RC was performed in 125 patients (27%), 55 for less than CR and 70 for superficial or invasive recurrence. Among patients with a CR, the 10-year actuarial rates for non-invasive, invasive, pelvic, and distant failure were 32%, 16%, 14%, and 29%, respectively. Median OS was 6.4 years. Five- and 10-year OS rates were 57% and 39% (T2 = 66%, 46%; T3-T4a = 41%, 26%), respectively. Five- and 10-year DSS rates were 66% and 59% (T2 = 75%, 66%; T3-T4a = 50%, 45%), respectively. In multivariate analyses, T2 disease (vs. T3-4; HR 0.55, 95%CI 0.40-0.76) and CR to induction therapy (HR 0.40, 95%CI 0.28-0.55) were significant predictors for improved OS. Age was not associated with DSS (HR 1.01, 95%CI 0.99-1.03). Conclusions: These data support the high rates of CR and bladder preservation in patients receiving CMT, and demonstrate long-term DSS similar to modern cystectomy series. CMT should be considered as an alternative treatment strategy for selected patients with MIBC.

Long-term Outcomes After Bladder-Preserving Combined Modality Therapy for Patients With Muscle-Invasive Bladder Cancer

Long-term Outcomes After Bladder-Preserving Combined Modality Therapy for Patients With Muscle-Invasive Bladder Cancer

EP-1060: Combined modality therapy of patients with gastric non-Hodgkin lymphoma. The update of long ñ term results

EP-1060: Combined modality therapy of patients with gastric non-Hodgkin lymphoma. The update of long ñ term results

Outcomes of combined modality therapy for patients with stage III or IV mediastinal malignant germ cell tumors

The treatment of primary mediastinal germ cell tumors with cisplatin-based chemotherapy followed by surgery is an established practice; however, the prognosis has remained poor. This study reviews the survival outcomes of patients with primary mediastinal germ cell tumors to evaluate the efficacy of our treatment. We retrospectively reviewed 11 consecutive patients with primary mediastinal germ cell tumors. We had treated four patients with seminomas and seven patients with non-seminomas. Ten patients had undergone cisplatin-based chemotherapy. All patients underwent complete resection. Two patients showed a failure of first-line chemotherapy and thus received salvage chemotherapies, including paclitaxel plus ifosfamide followed by high-dose carboplatin plus etoposide (TI-CE) with stem cell transplantation. One of them died of relapse 29 months later; while the other patient remained disease-free for 56 months postoperatively. The postoperative overall 3-year survival rates of the patients with non-seminomas and seminomas were 83 and 100%, respectively. Complete resection after establishing normalized or decreased at a low-level serum tumor markers plateau plays a crucial role in the management of patients with primary mediastinal malignant germ cell tumors.

Advances in combined modality therapy for patients with operable non-small cell lung cancer

非小细胞肺癌（non—small cell lung cancer，NSCLC）约占肺癌的80％～85％。目前，NSCLC的治疗手段主要有手术、放疗和化学药物治疗（包括靶向治疗）等，其中手术完全切除在可手术NSCLC（早、中期和部分局部晚期NSCLC）的治疗中起主导作用。近半个多世纪以来，虽然外科技术和手术器械日臻完善，但是肺癌外科切除术后患者的5年生存率长期徘徊在15％～45％。

Inhibition of the Notch-Hey1 Axis Blocks Embryonal Rhabdomyosarcoma Tumorigenesis

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood and remains refractory to combined-modality therapy in patients with high risk disease. In skeletal myogenesis, Notch signaling prevents muscle differentiation and promotes proliferation of satellite cell progeny. Given its physiologic role in myogenesis and oncogenic role in other human cancers, we hypothesized that aberrant Notch signaling may contribute to RMS tumorigenesis and present novel therapeutic opportunities. Human RMS cell lines and tumors were evaluated by immunoblot, IHC, and RT-PCR to measure Notch ligand, receptor, and target gene expression. Manipulation of Notch signaling was accomplished using genetic and pharmacologic approaches. In vitro cell growth, proliferation, and differentiation were assessed using colorimetric MTT and BrdU assays, and biochemical/morphologic changes after incubation in differentiation-promoting media, respectively. In vivo tumorigenesis was assessed using xenograft formation in SCID/beige mice. Notch signaling is upregulated in human RMS cell lines and tumors compared with primary skeletal muscle, especially in the embryonal (eRMS) subtype. Inhibition of Notch signaling using Notch1 RNAi or γ-secretase inhibitors reduced eRMS cell proliferation in vitro. Hey1 RNAi phenocopied Notch1 loss and permitted modest myogenic differentiation, while overexpression of an activated Notch moiety, ICN1, promoted eRMS cell proliferation and rescued pharmacologic inhibition. Finally, Notch inhibition using RNAi or γ-secretase inhibitors blocked tumorigenesis in vivo. Aberrant Notch-Hey1 signaling contributes to eRMS by impeding differentiation and promoting proliferation. The efficacy of Notch pathway inhibition in vivo supports the development of Notch-Hey1 axis inhibitors in the treatment of eRMS.

Is there a role for consolidative radiation therapy for aggressive B-cell lymphoma in the rituximab era?

Randomized trials have compared chemotherapy alone versus combined modality therapy in patients with aggressive non-Hodgkin lymphoma [1–7], with most of the trials focusing on patients with early-s...

Involved-Lesion Radiation Therapy After Chemotherapy in Limited-Stage Head-and-Neck Diffuse Large B Cell Lymphoma

To report treatment outcomes after combined-modality therapy in patients with Stage I/II head-and-neck (HN) diffuse large B cell lymphoma (DLBL). Eighty-six eligible patients received sequential chemotherapy and involved-lesion radiation therapy from 1995 to 2006. After a median of four cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or rituximab-plus-CHOP chemotherapy, a median of 41.4 Gy was delivered to the known initial gross lesion with adequate margin (2 to 3 cm). After a median follow-up of 57 months, eight treatment failures were observed: distant metastasis in 8 patients; and locoregional failure in 4 patients. Among the 4 patients with locoregional failure, 3 presented with in-field failures, and 1 both in-field and out-of-field failure (contralateral neck). Rates of overall survival (OS) and freedom from progression (FFP) at 10 years were 74.1% and 88.9%, respectively. There was no severe side effect except 1 patient with Grade 3 mucositis during and after completion of radiation therapy. Multivariate analyses showed that absence of B symptom (p = 0.022) and normal lactate dehydrogenase (p = 0.017) were related to favorable OS, age >60 years (p = 0.033) was related to favorable FFP, and international prognostic index of 0 or 1 was related to favorable OS (p = 0.003) and FFP (p = 0.03). This study demonstrated that patients with Stage I/II HN DLBL did not need whole-neck irradiation. Involved-lesion radiation therapy might reduce radiation toxicity with favorable treatment results.

Osteosarcoma of the jaw/craniofacial bones: Outcomes following multimodality treatment

10511 Purpose: To evaluate outcomes for patients with osteosarcoma of the jaw/craniofacial bones treated with surgery or combined modality therapy (CMT) consisting of surgery and radiation therapy (RT). Methods: Retrospective analysis was performed on data for 119 patients with osteosarcoma of jaw/craniofacial bones who underwent definitive resection with or without RT between 1960 and 2007. Median age was 33 years (range, 7–77 years). Ninety-two (77%) underwent surgery alone while 27 (23%) were treated with CMT. Median RT dose was 60 Gy (range, 50–66 Gy). Kaplan-Meier method was used to calculate the actuarial curves for survival (OS), disease-specific survival (DSS), local recurrence (LR), distant metastatic relapse (DM), and complication rates; and the log-rank statistic was used to test for significance of differences between curves. Results: Median follow-up was 5.8 years (range, 0.25 to 44.5 years). The OS rates at 5 and 10 years were 63% and 55%, respectively. Corresponding DSS rates were 67% and 61% respectively. Surgical margin status (positive/uncertain vs. negative) was adversely prognostic for OS (p=0.0001) and DSS (0.0001). Stratified analysis by margin status showed that CMT compared to surgery alone improved OS (80% vs. 31%, p=0.02) and DSS (80% vs. 35%, p=0.02) for patients with positive/uncertain margins. Multivariate analysis showed that CMT for patients with positive/uncertain margins improved OS (p&lt;0.0001). Forty-four patients (40%) experience LR and 25 (21%) developed DM. There was no difference in DSS if relapse was isolated LR vs. DM (26% vs. 29%, respectively at 5 years, p=0.48) Local control (LC) rates were 59% and 57% at 5 and 10 years, respectively. The use of CMT vs. surgery alone significantly improved LC for patients with positive/uncertain margins (75% vs. 24%, p=0.006). The rate of surgical complications was 28% at 5 years. Rates of RT-associated complications were 40% and 47% at 5 and 10 years, respectively. Conclusions: RT in addition to surgery improves OS, DSS, and LC for patients with osteosarcoma of the jaw/craniofacial bones who have positive/uncertain surgical margins. Complication rates from surgery and RT are high, but LR is lethal in this disease. Morbidity risks must be weighed against the need to eradicate disease with primary local managmement. No significant financial relationships to disclose.

Cytologically Proven Meningeal Carcinomatosis in Patients with Lung Cancer: Clinical Observation of 34 Cases

Meningeal carcinomatosis (MC) is a rare neurologic complication of lung cancer. Occasionally, it is the initial presentation of lung cancer. The clinical features of MC exclusively in lung cancer patients have not been well identified and characterized. The purpose of this report is to disclose the clinical features, laboratory findings, treatment and survival of patients with MC from lung cancer. We reviewed the medical records of 34 lung cancer patients with cytologically diagnosed MC at National Taiwan University Hospital from 1992 to 2002. Clinical symptoms and signs, cerebrospinal fluid parameters and lung cancer staging at the time of presentation were summarized. Previous treatment modalities for lung cancer, various treatments and response of MC, complications and survival times were also analyzed. Cerebrospinal fluid cytology revealed adenocarcinoma in 32 patients, and small cell carcinoma and squamous cell carcinoma in one each. MC occurred in approximately 0.7% of lung cancer patients. Nine patients had MC as the initial presentation of lung cancer. Symptom improvement was found in six patients who had whole brain irradiation for MC and one patient who had a ventriculoperitoneal shunt. Two of the patients with whole brain irradiation survived for longer than 1 year. Survival from cytologic diagnosis of MC ranged from 1 day to 82 weeks (median, 5.1 weeks). There was no difference in survival between patients treated by whole brain irradiation and other treatment modalities. The prognosis of MC from lung cancer is poor. A prospective study is needed to establish the effectiveness of combined modality therapy for patients with MC from lung cancer.

Carcinoma Metastatic to Cervical Lymph Nodes From an Occult Primary Tumor: The Outcome After Combined-Modality Therapy

The aim of this retrospective analysis was to analyze the results of treatment of patients with cervical node metastases from carcinoma of occult primary with a policy including neck dissection and postoperative comprehensive radiotherapy. Ninety patients were treated with curative intent from 1990 to 2002. The actuarial rate of neck disease control was 68.8% at 5 years (95% confidence interval [CI], 58.9%-78.7%). On multivariate analysis, the rate of neck disease control was significantly related to lymph nodal metastatic level (P = .006). The actuarial rate of developing head and neck primary tumors at 5 years was 8.9% (95% CI, 2.6%-15.2%). The 5-year actuarial rate of distant metastases was 19.1% (95% CI, 9.4%-28.9%). In multivariate analysis, a statistically significant difference in the rate of distant metastasis was obtained when patients were stratified according to the level of nodal involvement (P = .01) and the presence of extracapsular extension (P = .013). At the time of analysis, 50 of the 90 patients were alive. A total of 32 (35.6%) had died from causes related to their primary disease. Actuarial disease-specific survival at 2 and 5 years was 73.6% (95% CI, 64.3%-82.9%) and 62.8% (95% CI, 51.9%-73.7%), respectively. In multivariate analysis, a statistically significant difference in disease-specific survival was obtained when patients were stratified according to the level of nodal involvement and the presence of extracapsular extension. Our study seems to support the use of combined-modality therapy in patients with neck metastases from carcinoma of occult primary. However, in the absence of randomized trials, comprehensive irradiation cannot be routinely advised.

Hodgkin Disease/Lymphoma Clinical Practice Guidelines

Cure rates for Hodgkin disease/lymphoma have increased to such an extent that the overriding treatment considerations often relate to long-term toxicity, especially for patients with early- or intermediate-stage disease. Current management programs are based on comprehensive clinical staging followed by combined modality therapy for patients with favorable and intermediate prognosis, or chemotherapy alone for patients with advanced disease. Relapse is uncommon, but secondary management with peripheral stem cell transplantation may be effective. The excellent prognosis for these patients mandates careful long-term follow-up to detect late treatment effects. For the most recent version of the guidelines, please visit NCCN.org

Combined-modality therapy for patients with regional nodal metastases from melanoma

To evaluate the outcome and patterns of failure for patients with nodal metastases from melanoma treated with combined-modality therapy. Between 1983 and 2003, 466 patients with nodal metastases from melanoma were managed with lymphadenectomy and radiation, with or without systemic therapy. Surgery was a therapeutic procedure for clinically apparent nodal disease in 434 patients (regionally advanced nodal disease). Adjuvant radiation was generally delivered with a hypofractionated regimen. Adjuvant systemic therapy was delivered to 154 patients. With a median follow-up of 4.2 years, 252 patients relapsed and 203 patients died of progressive disease. The actuarial 5-year disease-specific, disease-free, and distant metastasis-free survival rates were 49%, 42%, and 44%, respectively. By multivariate analysis, increasing number of involved lymph nodes and primary ulceration were associated with an inferior 5-year actuarial disease-specific and distant metastasis-free survival. Also, the number of involved lymph nodes was associated with the development of brain metastases, whereas thickness was associated with lung metastases, and primary ulceration was associated with liver metastases. The actuarial 5-year regional (in-basin) control rate for all patients was 89%, and on multivariate analysis there were no patient or disease characteristics associated with inferior regional control. The risk of lymphedema was highest for those patients with groin lymph node metastases. Although regional nodal disease can be satisfactorily controlled with lymphadenectomy and radiation, the risk of distant metastases and melanoma death remains high. A management approach to these patients that accounts for the competing risks of distant metastases, regional failure, and long-term toxicity is needed.

Combined modality therapy for patients with nodal metastases from melanoma

7518 Background: Patients treated for regional nodal metastases from melanoma are at risk of distant metastases, regional failure, and long-term toxicity. Present treatment algorithms do not account adequately for these competing risks. Methods: Between 1983 and 2003, 466 patients with melanoma nodal metastases were managed with lymphadenectomy and radiation, with or without systemic therapy. For this retrospective review, actuarial outcomes were calculated using the Kaplan-Meier method and multivariate analysis was done with the proportional hazards model. Results: Of the 466 patients, surgery was a therapeutic procedure for clinically apparent nodal disease in 434. Adjuvant radiation was delivered to all patients, generally using a hypofractionated regimen, and systemic therapy was delivered to 154 patients. With a median follow-up of 4.2 years, 252 patients relapsed and 203 patients died of progressive disease. The 5-year DSS, DFS, and DMFS rates were 49%, 42%, and 44%, respectively. By multivariate analysis, increasing number of involved lymph nodes and primary ulceration were associated with an inferior 5-year disease-specific and distant metastasis-free survival. For patients with more than 10 involved LN the 2-year rate of brain failure approached 45%. The 5-year regional (in basin) control rate for all patients was 89% and on multivariate analysis there were no patient or disease characteristics associated with inferior regional control. The 5- and 10-year rates of symptomatic lymphedema were 9% and 11%, respectively, and varied according to nodal region. For patients with cervical, axillary or groin LN disease the corresponding rates of symptomatic lymphedema were 1%, 20%, and 27%, respectively (p <0.0001). Conclusions: Although regional nodal disease can be satisfactorily controlled with lymphadenectomy and radiation, the risk of death from melanoma remains high and patients requiring groin irradiation are at risk of chronic lymphedema. The data indicate that the threshold for recommending aggressive regional therapy should account for the site of nodal disease and certain clinical-pathologic factors. Also, clinical investigation must focus on the high rate of brain failure in some of these patients. No significant financial relationships to disclose.

Neck dissection in the combined-modality therapy of patients with locoregionally advanced head and neck cancer.

The purpose of this study was to evaluate the role of neck lymph node (ND) in the combined dissection modality therapy for locoregionally advanced head and neck. We identified patients with N2-N3 head and neck cancers who were enrolled in three consecutive multicenter phase II studies of concurrent chemoradiotherapy utilizing 5-fluorouracil and hydroxyurea on an alternate-week schedule with radiotherapy twice daily plus either cisplatin (C-FHX) or paclitaxel (T-FHX). Patients with unknown primary tumors, nasopharyngeal or paranasal sinus primaries, nonsquamous histology, progression or death during therapy, or incomplete therapy were excluded. A total of 131 patients were analyzed. Seventy-nine percent had N2 stage. ND was performed in 92 patients (70%), either prior to enrollment (n = 31) or after chemoradiotherapy (n = 61). With a median follow-up of 4.6 years, the 5-year locoregional and neck progression-free survival (PFS) rates were higher in patients with ND versus patients without ND: 88% versus 74% (p =.02) and 99% versus 82% (p =.0007). respectively; there was also a trend toward improved overall survival (OS) with ND, but PFS and distant PFS were comparable. In the subset of patients with N3 disease, ND was associated not only with better locoregional control but also with improved distant PFS. However, in patients with clinical complete response (n = 92), no significant differences in PFS (68% vs 75% at 5 years, p =.53) or any other survival parameters with or without ND were observed. ND improves neck control and is required for patients with clinically residual disease or N3 neck cancer but has no significant impact on the outcome of patients with N2 stage disease who are rendered clinically disease-free with intensive concurrent chemoradiotherapy.