Use Of Combined Modality Therapy Research Articles

Patterns of failure in locally advanced female breast carcinoma treated with neoadjuvant chemotherapy followed by surgery and radiotherapy – A prospective study

Background: The use of combined modality therapy including surgery, chemotherapy, and radiotherapy increases five survival rates in stage IIA and stage IIIB disease to 80% and 45%, respectively. Neoadjuvant chemotherapy (NACT) eradicates micro metastasis present in the body and also improves resectability. Aims and Objectives: The main aim of this study was to determine the locoregional recurrence and distant recurrence rates and thereby define clinical and pathological predictive factors for recurrence. Materials and Methods: This was a single institutional prospective study carried out in the Department of Radiotherapy, RG Kar Medical College and Hospital, Kolkata. From January 2017 to December 2019, according to inclusion and exclusions criteria, a total of 1183 histologically and/or cytologically proven breast carcinoma patients were included in this prospective study. Results: Breast conservative surgery was done in 16.5% of patients and the rest of the patients underwent modified radical mastectomy. Seven patients had undergone toilet mastectomy with the specimen. From the pathological review of the surgical specimens, 15.0% of patients achieved pathological complete response, while 19.4% of patients had clinical complete response. A total of 150 patients out of 1183 patients (12.67%) had disease recurrence. Conclusion: Local treatments, either surgery alone and/or RT alone, are inadequate therapies for locally advanced breast cancer patients, and multidisciplinary treatment should be used, to reach better management. Inoperable locally advanced breast carcinoma can be converted into operable by NACT.

The Impact of Chemoradiotherapy on Biophysical Properties of Glioblastoma Utilizing a Novel Murine Model

<h3>Purpose/Objective(s)</h3> Glioblastoma, historically viewed as a single disease entity, is now known to be composed of various subtypes. Here, we present our work evaluating the effects of chemoradiotherapy on cellular biophysical processes using a novel murine model of glioblastoma developed by our group. <h3>Materials/Methods</h3> Primary tumor cell lines were established from a murine glioma model generated from a synthetic DNA transposon system delivered oncogenic drivers SV40-LgTA and either NRASV12 or PDGFB. We have previously shown these cell lines, termed NRAS and PDGF, respectively, recapitulate the mesenchymal and proneural tumor subtypes. Treatment was administered with temozolomide (TMZ) to a maximum of 100µM, single fraction radiation therapy (RT) to a maximum of 10 Gy, or both. Cells were stained with Hoechst dye, imaged with an epifluorescence microscope with 10X objective lens, and counted with an image segmentation algorithm daily for 4 days to estimate cell survival and proliferation. On post-treatment day 4, surviving cells were plated on Matrigel coated 9.3kPa polyacrylamide gel and imaged with an inverted, transmitted light microscope with 10X objective lens every 5 minutes for 4 hours. Single cell mean squared displacement (MSD) was measured from time lapse images via an image segmentation algorithm. The random motility coefficient (µ) was calculated by the relationship MSD(t) = 4µt, where t is time. Data was compared via the Kruskal-Wallis test with Bonferroni correction for multiple comparisons when appropriate. <h3>Results</h3> There was no significant difference in cellular death or proliferation between treatment and control arms for the PDGF cell lines. In the NRAS cell lines, TMZ alone did not induce cell death while RT (P < 0.01) and combined modality therapy (P < 0.01) yielded cellular killing in a dose dependent manner. Furthermore, RT-treated NRAS cells proliferated more slowly than non-treated cells (0.05 vs. 0.20 hr-1, P=0.04). Control NRAS cell lines migrated faster than their PDGF counterparts at baseline (3.82 vs. 0.73 µm2/hr, P<1E-5). Within each cell line, the use of combined modality therapy significantly reduced cellular motility (PDGF: 0.73 vs. 0.21 µm2/hr, P=0.008; NRAS: 0.65 vs. 3.82 µm2/hr, P<1E-5). RT monotherapy additionally reduced motility in NRAS cell lines (1.07 vs. 3.82 µm2/hr, P<1E-5) while no difference was observed in PDGF cells. TMZ monotherapy did not affect motility within either cell line. <h3>Conclusion</h3> We evaluated biophysical properties of a novel murine glioma model utilizing oncogenic drivers overexpressing NRASV12 or PDGFB which we have previously shown recapitulates the mesenchymal and proneural subtypes of human glioblastoma, respectively. Here, we observed phenotypic differences in cellular migration following RT and TMZ regimens which could have subtype-specific ramifications for radiotherapy dose and target volume delineation.

Radiation/Drug Interactions and the Combinational Effects of Tyrosine Kinase Inhibitors and Radiation Therapy in the Treatment of Cancer

Introduction: Progress in both the development of Tyrosine Kinase Inhibitors (TKIs) and modern radiation therapy (RT) have opened new horizons for the safe and effective treatments of cancer. Combination therapies of TKIs and radiation therapy have been evaluated with variable sequencing and dosing of both agents. Radiation therapy induces cellular damage to cancer and normal tissue DNA by the production of direct and indirect ionization leading to a cascade of biological events. These ultimately lead to potential loss of cellular reproductive capacity, cell death or impotency. Repair mechanisms of RT-induced cell damage require repair pathways dependent on TK. TKIs are key regulators of cellular function and signaling proteins that catalyze phosphorylation reactions of tyrosine molecules. The purpose of this study was to briefly review the basic biology of RT and TKIs and to review the modern literature pertaining to the toxic and therapeutic effects of their combination in the treatment of cancer based on preclinical and clinical data. Methods: A retrospective review of the basic biology of RT and TKIs with the aim of identifying their combined toxicity and benefit in the treatment of cancer was performed. A systematic search of the standard published radiotherapeutic, radiobiology, chemotherapy and radiotherapy texts, PubMed, Google Scholar, and Clinical Key using the search terms; TKI, RT and combination TKI and RT from 1985-2020 was employed. Data were abstracted from 222 entries from the literature published in English. Issues of toxicity and therapeutic efficacy were defined to evaluate the safe and effective use of combined modality therapy (CMT). Results: Few randomized studies were available for high-level recommendations. The combined treatment of cancer with TKIs and RT may have benefit for palliation, progression free survival, and potential survival under well-defined circumstances. Any benefit of combined therapy is accompanied by significant potential for enhanced radiation toxicity in addition to the baseline potential toxicities of both agents. Conclusion: The data reviewed suggest potential benefit from the CMT of TKIs and RT but at a significant risk of toxicity, which may include severe, hematological, cardiac, gastrointestinal, pulmonary and central nervous system toxicity. Further randomized prospective studies are necessary to define their safe and effective combined therapies. New TKI’s and radiotherapeutic modalities are constantly under development necessitating ongoing and often long term clinical evaluation to define benefits and risks.

Management of high-risk endometrial cancer: are we there yet?

Management of high-risk endometrial cancer: are we there yet?

Neoadjuvant chemoradiation for locally advanced resectable carcinoma of the esophagus: A single-center experience from India with a brief review of the literature.

The management of locally advanced carcinomas of the esophagus and esophagogastric junction has undergone a major evolution over the past two decades with the widespread use of combined modality therapy. Although many Indian centers practice the combined modality therapy with neoadjuvant chemoradiation (nCRT), published data are sparse. The objective of this study was to study the safety and efficacy of nCRT in patients with locally advanced resectable carcinoma of the esophagus. Prospective single-arm study of the first fifty patients enrolled over 3 years (2014-2016). The median age was 51 years (M:F = 3:2), 90% of the patients had squamous cell carcinomas, and 69% had lower-third lesions. All accrued patients completed the intended dose of radiation; however, approximately 20% had a treatment delay, which was duly gap corrected. Importantly, there were no treatment-related toxic deaths. Eleven patients could not undergo surgery following nCRT (two patients defaulted, two were deemed medically unfit, and seven (14%) patients had disease progression on imaging). Thirty-nine (78%) patients were planned for definitive surgery; however, a further 7 (14%) were found to be inoperable intraoperatively. Thirty-two patients successfully completed their definitive surgical procedures with R0 resections, of which 19 patients (38%) had a pathological complete response (pCR). There was no postoperative 90-day mortality in our study cohort. Analysis of prognostic factors that predicted a response showed that patients who had adenocarcinoma and with circumferential lesions responded poorly. nCRT appears to be a safe and a reasonably well-tolerated option in carefully selected patients with resectable locally advanced esophageal cancers. Although our data are not mature to analyze the survival outcomes with a pCR rate of 38%, it suggests nCRT to be a promising option in the management of locally advanced resectable esophageal cancers.

Consolidative Radiation in DLBCL: Evidence-Based Recommendations.

Radiation therapy (RT) has been described as the most effective single agent in the treatment of lymphoma; however, contemporary lymphoma treatment rarely relies on single agents. In the modern era, the selection of appropriate patients for combined modality therapy has become increasingly complex over the last decade with the transition to immunochemotherapy, the emergence of functional imaging for response evaluation, and the improvement in conformal avoidance of normal tissues when delivering RT. Recent evidence demonstrates that selected patients with DLBCL have significantly better outcomes when RT is added to immunochemotherapy; however, there are important knowledge gaps regarding the use of functional imaging to facilitate treatment selection. This article will review the current evidence regarding the optimal use of combined modality therapy for DLBCL.

National Patterns of Care and Outcomes After Combined Modality Therapy for Stage IIIA Non–Small-Cell Lung Cancer

The role of surgery in addition to chemotherapy and radiation for stage IIIA non-small-cell lung cancer (NSCLC) remains controversial. Because there are limited data on the benefit from surgery in this setting, we evaluated the use of combined modality therapy nationally and explored the outcomes with and without the addition of surgery. Patient variables and treatment-related outcomes were abstracted for patients with clinical stage IIIA NSCLC from the National Cancer Database. Patients receiving chemotherapy and radiation were compared with those undergoing chemotherapy, radiation, and surgery (CRS) in any sequence. Between 1998 and 2010, 61,339 patients underwent combined modality treatment for clinical stage IIIA NSCLC. Of these, 51,979 (84.7%) received chemotherapy and radiation while 9360 (15.3%) underwent CRS. Patients in the CRS group were younger, more likely female patients and Caucasians, and had smaller tumors and lower Charlson comorbidity scores. The 30-day surgical mortality was 200 of 8993 (2.2%). The median overall survival favored the CRS group in both unmatched (32.4 months versus 15.7 months, p < 0.001) and matched analysis based on patient characteristics (34.3 versus 18.4 months, p < 0.001). There is significant heterogeneity in the treatment of stage IIIA NSCLC in the United States. Patients selected for surgery in addition to chemoradiation therapy seem to have better long-term survival.

Challenges With the Diagnosis and Treatment of Cerebral Radiation Necrosis

The incidence of radiation necrosis has increased secondary to greater use of combined modality therapy for brain tumors and stereotactic radiosurgery. Given that its characteristics on standard imaging are no different that tumor recurrence, it is difficult to diagnose without use of more sophisticated imaging and nuclear medicine scans, although the accuracy of such scans is controversial. Historically, treatment had been limited to steroids, hyperbaric oxygen, anticoagulants, and surgical resection. A recent prospective randomized study has confirmed the efficacy of bevacizumab in treating radiation necrosis. Novel therapies include using focused interstitial laser thermal therapy. This article will review the diagnosis and treatment of radiation necrosis.

Disparity in the use of combined modality therapy for rectal cancer in the older adult

The standard treatment strategy for patients with rectal adenocarcinoma having T3 or T4 tumors or positive lymph nodes includes concurrent chemoradiation, surgery and chemotherapy. Population based studies show relatively low rates of usage of standard therapy for rectal cancer in the older adult. Two decades of cases of stage II and stage III rectal cancer from two academic teaching hospitals were reviewed. Comparisons were made of subjects ≤70 or ≥71years with regard to initiation and completion of radiation, chemotherapy and surgery. Subjects ≥71years of age had significantly lower proportions of surgical resection (84 vs. 94%) and of initiation of all three component of standard therapy (49 vs. 66%) compared to those ≤70years of age. Subjects ≥71years had significantly more co-morbidities; however, the difference in initiation of therapy remained after adjusting for stage, treating hospital, co-morbid status, race or sex in multivariable analysis. The odds for initiation of therapy were reduced by ≈22% in older adults in the adjusted analysis. Among all patients who started therapy only 56% completed it without dose reduction or delay. There were trends to increased completion among those receiving neo-adjuvant vs. post-operative chemoradiation and among those with stage III as opposed to stage II cancer. Our study indicates that a major disparity in the use of standard therapy for rectal cancer in the older adult exists in academic hospital settings. It will be important for oncologists to reconsider increasing the usage of curative therapy in these patients.

The management of high-risk, locally advanced, prostate cancer radiation therapy

The management of high-risk, locally advanced, prostate cancer radiation therapy

Hodgkin's lymphoma therapy: past, present, and future

Importance of the field: The treatment of Hodgkin's lymphoma (HL) with the use of radiotherapy and systemic chemotherapy has been one of the success stories of modern oncology. HL therapy has been the paradigm for the systematic evaluation of different curative modalities, resulting in cure for the majority of patients. The current focus is on designing initial therapeutic strategies that retain efficacy and minimize long-term toxicity. Appropriate use of pathologic, clinical, biologic and radiologic prognostic factors in identification of aggressive HL is paramount in designing a successful therapeutic strategy.Areas covered in this review: This review addresses the current and future use of prognostic tools, including PET scanning and other biomarkers, in identifying patients with aggressive HL, with reference to publications from the last two decades. The current standard approaches with the use of combined modality therapy and systemic chemotherapy as well as the promising role of future response-adapted strategies is reviewed.What the reader will gain: The reader will obtain a comprehensive review of risk assessment strategies as well as current and investigational therapeutic approaches in the management of HL.Take home message: In HL, appropriate utilization of risk assessment strategies is required to maximize therapeutic outcomes while minimizing toxicity, especially long-term toxicity. Response-adapted therapy utilizing PET has the potential to profoundly improve the therapeutic landscape in HL.

Reduced-Intensity Therapy for Early-Stage Hodgkin Lymphoma

The use of combined-modality therapy — doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) plus involved-field radiation therapy (IFRT) — yields a high cure rate for patients with stage I or II Hodgkin lymphoma (HL). However, each of these modalities poses risks for acute and delayed toxicities. At the American Society of Hematology 2009 meeting, the German Hodgkin Study Group reported preliminary results of a multicenter trial (HD10) showing that therapy de-escalation minimized treatment-related complications yet retained high cure rates in early-stage HL …

Sacral metastases in an endometrial cancer patient after treatment with sequential chemo-radiotherapy: A case report

The incidence of bone metastases in endometrial cancer is reported to occur in less than 15% of patients with metastatic disease. The medical literature is limited to only case reports, although none describing a sacral recurrence after adjuvant chemo-radiation therapy. We present the case of a 64-year-old woman who underwent surgery for endometrial adenocarcinoma followed by 'sandwich' chemoradiation therapy at our institution, July 2006 (FIGO stage IB grade 3). In spite of adjuvant therapy, which was delivered in August 2008 the patient, developed an isolated sacral recurrence. The optimal therapeutic modality for endometrial cancer patients with high-risk disease remains controversial. The increasing use of combined modality therapy for early stage, high-risk patients may produce different recurrence patterns than described in historical controls.

Postablative Reconstruction Is Better Terminology than Oncoplastic Surgery

Sir: Art, indeed, consists in the conception of the result to be produced before its realisation in the material. —Aristotle in De Partibus Animalium (On The Parts Of Animals), 350 BC Ongoing innovations continue to advance effective surgical primary tumor control and are linked to improved surgical outcomes, minimized patient morbidity, and better quality of life. The term “oncoplastic” was first used in 1996.1,2 It originates from the Greek words onkos (ογκοσ), meaning bulk, mass, or tumor; and plastikos (πλαςτικóσ), meaning molded or shaped. These words together mean the molding of a tumor. This term is therefore unsatisfactory when applied to the combination of oncology surgery and plastic surgery. Surgery is the oldest modality of cancer therapy and still forms the mainstay of treatment for solid tumors. Surgery operates by zero-order kinetics, in which all excised cells are killed. Ablation derives from the Latin ablatus, the irregular past participle of auferre, to carry away (ab-, away; plus latus, carried); it now has a specifically surgical edge, and today it applies principally to the surgical removal of any part of the body.3 During the past two decades, major improvements in both operative technique and the use of combined-modality therapy have significantly reduced the morbidity and mortality associated with the surgical treatment of solid neoplasms. For example, breast-preserving surgery has become an alternative to mastectomy in patients with breast carcinoma, and limb salvage is often possible in patients with bone and soft-tissue sarcomas. Advances in microvascular surgery now permit the free transfer of complex autologous tissues, such as free jejunal grafts to reconstitute the upper aerodigestive system or osteomyocutaneous flaps to reconstruct extremities and other mobile body parts such as the jaw. Intuitively, it appears logical that the term “postablative reconstruction” is an appropriate term for the specialized art of surgery devoted to the restoration of form and function after the surgical removal of solid tumors. Sammy Al-Benna, M.R.C.S., Ph.D. Lars Steinsträßer, M.D. Klinik für Plastische Chirurgie und Schwerbrandverletzte BG Kliniken Bergmannsheil Ruhr-Universität Bochum, Germany

Combined Modality Therapy for Lacrimal Sac Malignancy

Tumors of the lacrimal sac are uncommon and carry a high rate of malignancy. These neoplasms have a tendency to spread along the lacrimal drainage system, which must be radically excised for improved outcomes. We report our experience of combined modality therapy for two cases of lacrimal sac malignancy. The first was a 50-year-old man who presented with a basaloid squamous cell carcinoma occupying the medial orbit, displaying an infiltrative growth pattern and abutting the globe on CT and MR images. The tumor responded dramatically to two cycles of paclitaxel-cisplatin-fluorouracil chemotherapy, allowing for a conservative surgical resection. The second case was an 80-year-old man with adenoid cystic carcinoma arising from the lacrimal sac with involvement of medial orbital contents. In both patients, a limited exenteration of medial orbital contents was performed, along with a medial maxillectomy. Adjuvant therapy with cisplatin chemoradiation was administered to the first patient and only radiation to the second. In this report, we highlight the benefits of combination therapy, our approach of partial exenteration of medial orbital structures with medial maxillectomy, the mode of reconstruction, and the functional results. We conclude that satisfactory cosmesis and function may be maintained in patients with aggressive lacrimal sac malignancies with the use of combined-modality therapy.

Combined Modality Therapy in the Elderly Population

The incidence of cancer among older patients continues to rise. The use of combined modality therapy has improved survival in a variety of malignancies, including rectal, head and neck, and lung cancer; however, the addition of chemotherapy increases substantially the toxicities of treatment. Elderly patients have generally been excluded from prospective clinical trials and as such, there is a lack of evidence-based data with regards to the most appropriate treatment. Age itself should not be used as a criterion for foregoing combined modality therapy in elderly patients. Due to the increased toxicity of therapy, patients must be carefully selected. Any medical intervention should account for life expectancy, performance status, tolerance to therapy, and presence of medical or social conditions that may impact therapy. We encourage a comprehensive geriatric assessment to evaluate functional status, comorbidities, mental status, psychological state, social support, nutritional status, polypharmacy, and geriatric conditions in order to improve a patient's overall functional status during the course of therapy. Fit elderly patients should be considered candidates for combined modality therapy, however, because they are potentially more vulnerable to therapy, careful attention should be paid to hydration and nutritional status with early intervention when necessary. Investigators should be encouraged to expand eligibility to include elderly patients on non age-related clinical trials. Additionally, therapy-related clinical trials directed at the elderly should be developed.

A Look in the Mirror

A Look in the Mirror

Treatment of Stage IIIa Hodgkin's Disease: Long Follow-Up Perspective

Meticulous attention to detail, clinical research, and a degree of therapeutic empiricism set the stage for the spectacular improvements generated in the long-term outcome of Hodgkin’s disease in the 1960s and 1970s. The results below are a reflection of this, documenting the commitment of the generation of academic physicians pioneering hematologic oncology 40 years ago. At the time, management was based on the Ann Arbor Staging Classification based on the presumed anatomic spread of the disease, the outcome potential of megavoltage irradiation, and the assumption that systemic chemotherapy was substantially more toxic—and as yet—unproven in efficacy, hence reserved for advanced disease. It was generally accepted that disease localized to one side of the diaphragm should be treated with irradiation, at least to a mantle or inverted Y field, that advanced and symptomatic disease be treated with cyclical combination chemotherapy, and that asymptomatic nodal disease on both sides of the diaphragm (stage IIIA) receive either total nodal irradiation, chemotherapy, or both. Over time, it became clear that bulky disease and multiple nodal sites were poor prognostic factors, and combined chemoradiotherapy became the treatment of choice for those in whom they were identified. By 1974, at least at St. Bartholomew’s Hospital, 40% of patients with stage II disease were being treated this way. The article above reported interim data on a subset of patients, all identified as having pathologic stage IIIA disease on the basis of Ann Arbor Classification, including staging laparotomy, representing approximately 20% of the patients seen during the period in question. In 2008, more than a quarter of a century after the first patient was treated, none have been lost to follow-up. Forty percent are alive in first remission, presumed cured, with an additional 13% currently disease-free in a second remission for more than 3 years. The outcome was the same for both substages (IIIA1, IIIA2) and both combination chemotherapy and total nodal irradiation. This extraordinary improvement over the natural history of the disease, achieved over a short time, is only marred by a less-than-satisfactory overall survival pattern due, at least in part, to late toxicity. These data mirror the overall outcome of therapy seen in the newly diagnosed population of patients treated at St. Bartholomew’s Hospital from 1968 to 1985, only 12 having been lost to follow-up. Based on the Ann Arbor Stage, 526 adults were treated with mantle or inverted Y irradiation, combination chemotherapy with mustine, vinblastine, prednisolone, and procarbazine, or combined modality treatment with 55% undergoing laparotomy. The management at recurrence depended on the circumstances, but only included myeloablative chemotherapy in 9 patients. With only 12 lost to followup, 49% are alive, 39% in first remission for a minimum of 23 years, and an additional 10% have been in second or subsequent remission for at least 5 years. Twenty percent have died of Hodgkin’s disease and 31% have died resulting from other causes (including second malignancy 9%, cardiac event 9%; Table 1; Fig 1). Age and stage were highly statistically significant prognostic factors (P .001 and P .001, respectively; Fig 2, Fig 3). Within stage III, both the absence of B symptoms (P .01) and laparotomy staging (P .01).were favorable factors. In 2008, both investigation of the patient with Hodgkin’s disease and the treatment are substantially different, and better. Lymphography has been replaced by computed axial tomography, to the enormous benefit of the patient in terms of comfort. Laparotomy has become redundant both through the identification of surrogate markers of extensive disease obviating the need for diagnostic splenectomy and lymph node mapping, and the increasing use of combined modality therapy, which obviates the necessity for demonstrating limited anatomic spread. The most recent addition to the imaging

Thyroid lymphoma: A single institution’s experience

18533 Background: Extranodal lymphomas account for a significant proportion of non-Hodgkin’s lymphomas. Thyroid lymphoma accounts for &lt;2% of these. Lymphoma represents approximately 2% of all malignant thyroid tumours and is almost always of B-cell lineage. The main presenting symptom is a rapidly enlarging goiter and approximately half present with disease limited to the thyroid gland, designated stage IE. Due to its rarity, there is limited information with regard to prognosis or management. Pre-existing chronic autoimmune (Hashimoto’s) thyroiditis is the only known risk factor. Methods: We retrospectively reviewed all cases of thyroid lymphoma found in our institution over a 15 year period (1985–2000). Eleven patients were identified as suitable for analysis. Diagnosis and staging involved a full history and physical examination with relevant serology. Radiological imaging included computerized tomography, plain radiographs and ultrasound. Bone marrow aspirate and biopsy were performed in ten of the patients and patients were then staged according to the Ann Arbour Classification. We specifically analysed patients for their epidemiological features, presentation, treatment and their overall outcome. We compared our data to those from earlier series. Results: Seven of the 11 patients were female with a median age of diagnosis of 56. Most patients complained of neck swelling for a number of months but dysphagia, dyspnoea and hoarseness (80%) were the symptoms that prompted presentation. Hashimoto’s thyroiditis was not found. The commonest histological subtype was diffuse large B cell lymphoma (45% of cases). Seven patients had stage I disease, 3 stage II and 1 stage IV. Nine patients received chemotherapy and radiotherapy was administered in the adjuvant setting to nearly half of the patients. No correlation between presentation and other diagnostic tests or survival was found. Two-year survival for our patients was 100% and no cases died from their disease. Conclusion: Thyroid lymphoma is a rare disease and valuable information on this subject has been provided by single institution studies. Our encouraging survival figures are likely a combination of the predominance of early stage disease and the use of combined modality therapy. The use of monoclonal antibodies may provide a further benefit to these patients. No significant financial relationships to disclose.

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.