Change In Treatment Strategy Research Articles

Monitoring the Progressing Glaucoma Patient – What Are the Challenges?

Diagnosing glaucoma progression is complex. It is essential to assess both structure and function to detect progression. Establishing a reliable baseline is crucial in this process. A functional baseline requires repeated visual field testing. Documentation of the optic disc appearance is necessary for the acquisition of the structural baseline. This can be achieved by the complementary modes of both clinical and imaging devicebased optic disc documentation. Imaging-based methods to assess progression and rate of progression are likely to prove important in the future, but currently more guidance for their use in clinical practice is required. Rate of progression provides important information about the risk of vision loss. Guidelines therefore recommend determining the rate of progression for the individual patient when planning management. Adherence issues need to be addressed before changing treatment strategy, since poor compliance may play a considerable role in the progression of disease in many patients. In conclusion, we must strive to improve the management of glaucoma to limit the impact disease progression has on the patient’s quality of life.

Chemotherapy for Colorectal Cancer

Recent advances in chemotherapy lead to improved survival outcomes in patients with colorectal cancer. The 5-fluorouracil (5-FU) is still one of the important chemotherapeutic agents since 1950s, but the introduction of newer cytotoxic agents, irinotecan and oxaliplatin, or targeted agents, bevacizumab and cetuximab, have changed treatment strategies for these patients. A deliberate choice should be made for adjuvant chemotherapy, because it has became complicated more than ever before. Oxaliplatin plus 5-FU seemed to be superior in terms of disease-free and overall survival than 5-FU alone after curative surgery for colon cancers. However not all of these patients seemed to receive benefit from this intensive adjuvant treatment, and some limitations are present according to the postoperative stage, tumor biology and clinical characteristics. For metastatic disease, there is no doubt that more complicated strategies are present because we have more abundant chemotherapeutic agents available for metastatic setting compared to adjuvant setting. Recently, targeted agents, such as bevacizumab or cetuximab, also took an important place in the treatment of metastatic colorectal cancer, and many efforts are also made to find the biomarkers for predicting treatment responses to these targeted agents. In this review, we intended to sort up the standard strategies of chemotherapy for patients with colorectal cancer according to the latest pivotal publications.

Synchronous Hepatic Metastases from Colon Cancer: Changing Treatment Strategies and Results of Surgical Intervention

More effective chemotherapeutic agents have broadened the role of hepatic resection in the management of patients with synchronous hepatic metastases from colon cancer. This study examines the management patterns and the role of hepatobiliary surgical evaluation in patients with synchronous stage IV colon cancer. Patients with synchronous hepatic metastases from colon cancer evaluated and treated from 1/99 to 11/04 were analyzed retrospectively. Demographic, disease-related, and treatment-related variables were reviewed and correlated with disease-specific survival (DSS). One hundred and fifty-one patients were evaluated. The majority of patients (60%) were first evaluated by a medical oncologist while 34% were first evaluated by a hepatobiliary surgeon. Ultimately, 128 patients (85%) underwent surgical evaluation and 77% of those evaluated underwent surgical intervention. Patients who underwent operative exploration +/- debulking had less hepatic disease but also received more chemotherapy than patients not explored and those who never underwent hepatobiliary surgical evaluation. Sixty-eight patients (53%) who underwent hepatobiliary surgical evaluation underwent hepatic resection. Negative independent predictors of hepatic resection were bilobar metastases and extrahepatic disease found during exploration. Variables associated with improved DSS included: carcinoembryonic antigen level < or =200 ng/ml, node-negative primary tumor, < or =4 liver metastases, unilobar metastases, largest metastasis < or =5 cm, and hepatic resection. Five-year DSS following hepatic resection was 54%. We conclude that hepatobiliary surgical evaluation of patients with synchronous hepatic metastases is warranted since many are candidates for hepatic resection. A multidisciplinary treatment approach which combines both medical and surgical modalities may be associated with improved survival.

Value of [18F]Fluorodeoxyglucose Positron Emission Tomography in the Management of Follicular Lymphoma: The End of a Dilemma?

Background[18F]Fluorodeoxyglucose (FDG) positron emission tomography (PET) is a powerful tool for the imaging of various lymphomas. Despite its high FDG avidity, there is little data on PET in follicular lymphoma (FL). In this work, we present findings concerning PET at staging and posttreatment evaluation in FL. Patients and MethodsA total of 181 PET scans were evaluated in 117 patients with FL in a retrospective study. Positron emission tomography—based results were compared with conventional staging in 82 patients. Posttreatment PET evaluation was performed in 99 patients; there were comparable progression-free survivals of PET-positive and PET-negative patients. ResultsPositron emission tomography showed more involvement than computed tomography (CT) with clinical examination in 41 of 82 patients (50%), less in 11 of 82 (13%); the same extension was found in 27 of 82 patients (33%), and 3 patients revealed discordant foci visible on PET only and lymphadenopathy without PET activity (P < .001). Including the results of trephine biopsy, PET finally upstaged FL in 15 of 82 patients (18%), which was projected in change of treatment strategy. There were 73 of 99 negative posttreatment PET scans; 54 of 73 PET-negative patients (74%) remain in complete remission (median follow-up, 27 months); 19 (26%) of them relapsed with median of 12 months. Fourteen of 20 (70%) PET-positive patients relapsed with a median of 4.5 months regardless of findings on CT and subsequent therapy. The difference in relapse rates between PET-positive and PET-negative patients is statistically significant (P < .001). ConclusionPositron emission tomography at staging is able to substantially change treatment strategy in an important proportion of patients with FL. Persisting PET positivity after treatment predicts for a high risk of an early relapse and can identify patients with poor prognosis.

Role of radiotherapy in the management of acromegaly

Active acromegaly can be treated effectively by transsphenoidal surgery, radiotherapy and medical treatment in the form of somatostatin analogs and growth hormone receptor antagonists. Many patients will require a combination of treatment modalities to normalize growth hormone excess and associated increased mortality, and to improve comorbidity. Following postoperative radiotherapy, growth hormone and insulin-like growth factor-I levels gradually decrease and normalization of growth hormone and insulin-like growth factor-I is achieved in 50% of patients after 5 years and 75% after 10 years. Disadvantages of radiotherapy include the long interval until hormone levels have sufficiently decreased and the high incidence of radiation-induced hypopituitarism. Radiotherapy was associated with increased mortality in some but not other studies. Limitations in the design and confounding factors, such as years spent with active disease and changing treatment strategies, make it impossible to draw conclusions on this topic. Gamma knife radiosurgery may combine faster decline of growth hormone excess with a lower incidence of hypopituitarism in eligible cases, but long-term results of this radiation technique are lacking. At present, patients will preferentially be treated by primary surgery and/or somatostatin analog treatment, followed, if necessary, by growth hormone receptor antagonist treatment, while radiotherapy is reserved for selected cases only. The indications for radiotherapy and radiosurgery need to be revisited in the near future, when longer follow-up results for medical treatment and radiosurgery have become available. This review summarizes the recent literature on efficacy and side effects of radiotherapy and radiosurgery in acromegaly and discusses the place of radiation treatment in the treatment algorithm of acromegaly.

Changing Treatment Strategy for Gastrinoma in Patients with Zollinger‐Ellison Syndrome

We overviewed the recent development of curative surgery for gastrinoma that has been rapidly improved since the development of new localization techniques, especially the selective arterial secretagogue injection test (SASI test) and somatostatin receptor scintigraphy (SRS). A number of new pathological findings of gastrinomas in patients with Zollinger-Ellison syndrome have been accumulated in accordance with the increase of curative resection of gastrinomas, and these new findings also have contributed to the progress of the treatment strategy for grastrinomas.

Changing treatment strategy of cavernous sinus meningiomas: experience of a single institution

Background Oncological treatment of a neoplasm is more than surgical removal of the tumor. Probably, this truth is the reason for the ongoing discussion on cavernous sinus meningiomas in the last decade. Debate on optimal management of cavernous sinus meningiomas aims to compare the different treatment strategies: ( a) radical surgical resection and ( b) conservative surgical resection complemented with radiosurgical treatment. Materials and Methods Natural history of the change in the management strategy of cavernous sinus meningiomas in our department before and after GK facility became available in 1997 allowed us to compare the 2 aforementioned strategies. Before installation of a Leksell GK unit at the hospital in 1997, the neurosurgical team at Marmara University Institute of Neurological Sciences and Faculty of Medicine (Istanbul, Turkey) treated patients with cavernous sinus meningioma using radical resection (radical strategy, group A, 10 patients). After 1997, the same neurosurgical team used understanding of surgical removal of the extracavernous sinus tumor component with GK irradiation of the intracavernous part (conservative strategy, group B, 12 patients). Another group of patients, who were treated with GK as a first-step treatment, was analyzed (GK group, group C, 26 patients). Results At the end of the third year, more stable tumor volume control was achieved in groups B and C; after the second year, an incline in the tumor volume-time graph was detected. Group B resulted in less cranial nerve–related complications; a certain degree of improvement in cranial nerve deficits was observed. Conclusion Comparing 2 different management strategies for cavernous sinus meningiomas in the same hospital setting using the same neurosurgical group, we conclude that extracavernous resection followed by GK is as effective as radical surgery. Considering cranial nerve complications and third-year tumor volume control achievement, conservative approach yielded better results. Longer follow-up with larger series is necessary.

Perspectives for combination therapy to overcome drug-resistant multiple myeloma

The introduction of melphalan and prednisone 40 years ago was a significant advance in the treatment of multiple myeloma (MM). In the following decades, significant advances were few, but included landmarks, such as the introduction of VAD and autologous transplantation during the 1980s and bisphosphonates in the 1990s. Although response rates to therapy were increased, overall survival was not significantly improved. In 1999, the treatment of myeloma was revolutionized by the introduction of thalidomide. Subsequently, the development of the immunomodulatory thalidomide analogues and the proteasome inhibitor bortezomib have impacted on response rates to therapy in relapsed and refractory myeloma and are currently being evaluated as primary therapy for myeloma. Early results suggest activity in combination with standard therapy to overcome drug resistance in patients with early stage disease and are changing treatment strategies in multiple myeloma. As an increasing number of other novel therapeutics is identified and mechanisms of resistance are elucidated, combinations of these drugs will be developed to optimize new therapeutic regimens.

Linac radiosurgery as a tool in neurosurgery

Stereotactic radiosurgery is a radiation technique that uses a high radiation dose focused on a stereotactic defined intracranial target in single fraction with high precision. In the 1980s, linear accelerators were introduced as a tool for radiosurgery beneath the already accepted gamma unit. Technique and mechanical precision of LINACs have become equal to the gamma unit and LINAC radiosurgery became more and more used recently. From January 1996 to August 2003 we have treated 237 patients with LINAC radiosurgery. A combination of the University of Florida system and the X Knife System, developed by Radionics, was used in all patients. A number of 110 patients had 161 brain metastases treated, whereas the local tumor control rate was 89.4%. The 1-year survival rate was 54.9% with a median survival of 54 weeks. In 55 patients we have treated 57 meningiomas, mostly located at the skull base (37 out of 55 patients). Local tumor control rate in our patients with skull base meningiomas at 5-year follow up was 97.2%. In this time period, we have also treated acoustic schwannoma, glioma, pituitary adenoma, arteriovenous malformations and patients with trigeminal neuralgia. LINAC radiosurgery has become a daily tool in neurosurgery and changed treatment strategies especially in the treatment of brain metastases and skull base meningiomas towards a less aggressive and multimodality approach. It is not only an alternative to open surgery, but also a very effective adjuvant treatment modality in many neuro-oncological patients, which helps us to enhance tumor control rate, minimize morbidity and increase postoperative quality of life.

Dissemination patterns of pilocytic astrocytoma

Two patients with multifocal pilocytic astrocytoma diagnosed by magnetic resonance imaging (MRI) and confirmed by histopathological examination are reported. They presented distinct sites and mechanisms of metastasis: to distant ventricles through the cerebral spinal fluid (CSF) in patient 1 and to contralateral parenchyma, possibly through white matter tracts, in patient 2, a pathway not so far reported in pilocytic astrocytoma. Early detection of multifocal pilocytic astrocytoma by MRI may change treatment strategies and improve prognosis.

LINAC Radiosurgery in Skull Base Meningiomas

LINAC radiosurgery has provided increasing access and changed treatment strategies in patients with benign skull base meningiomas in recent years. From January 1996 to January 2003, 37 patients with skull base meningiomas were treated with LINAC radiosurgery. A combination of the University of Florida system and the X Knife System, developed by Radionics, was used in all patients. Eight patients were treated by microsurgical resection before radiosurgery, in two patients tumor recurrence was treated and in 29 patients LINAC radiosurgery was the initial treatment procedure. The median treatment volume was 5.9 mL (0.7 to 22 mL) and the median given dose was 14.6 Gy (12.8 to 18 Gy) prescribed to the 80 percent isodose line. The follow-up period is between 12 and 96 months, median 66 months. 12 patients (32.4 %) showed a significant reduction in tumor size, in 11 patients (29.7 %) there was significantly less contrast enhancement and in 13 patients (35.1 %) the skull base meningioma was without any change. In one patient (2.8 %) there was tumor growth 48 months after radiosurgery, so the tumor control rate was 97.2 %. Two patients (5.6 %) showed neurological worsening after radiosurgery, whereas the symptoms were transient in one patient. LINAC radiosurgery offers us an effective treatment modality and changes treatment strategies in skull base meningiomas towards a less aggressive surgical approach. By combining microsurgery and radiosurgery we can achieve high tumor control rates with an acceptable low morbidity and a high level of quality of life.

Is [18F]-2-fluoro-2-deoxy-d-glucose (FDG) scintigraphy with non-dedicated positron emission tomography useful in the diagnostic management of suspected metastatic thyroid carcinoma in patients with no detectable radioiodine uptake?

Dedifferentiation of thyroid cancer leads to an inability of thyroid cells to concentrate iodine. In these cases, imaging methods that allow an accurate detection of recurrence and/or metastases at an early stage are essential for an adequate management of patients. Positron emission tomography using [18F]-2-fluoro-2-deoxy-d-glucose and a dedicated (dPET-FDG) or non-dedicated (nPET-FDG) camera has been suggested as a potential tool for the detection of tumour foci. This prospective study was undertaken to evaluate nPET-FDG in 51 consecutive patients (18 men, 33 women) with differentiated thyroid cancer (33 papillary, 11 follicular, four insular and three oncocytic (Hurthle-cell) thyroid carcinomas). Selection criteria were high thyroglobulin (Tg) levels (>10 ng/ml off-levothyroxine treatment) and no detectable radioiodine uptake, on a whole body scan performed with a high dose, in the absence of iodine contamination. Results were interpreted in terms of assumed presence of tumoral tIssue. Sensitivity of nPET-FDG was similar to that of conventional imaging modalities (67%). False negative nPET-FDG (n=16) were observed mostly in cases of micro-lesions (lymph nodes or lung metastases). Conversely, nPET-FDG identified new tumoral sites in 11 cases. Better sensitivity was found for nPET-FDG in patients with Tg levels higher than 15 microg/l (P<0.05). On a patient basis, results of nPET-FDG were equivalent to that of dPET-FDG. Finally, nPET-FDG changed treatment strategy in seven patients. nPET-FDG has a high sensitivity for the detection of tumour sites in patients when pathological iodine uptake cannot be demonstrated and appears to be a useful method in patients with elevated Tg levels, especially when dedicated PET is either unavailable or impractical.

A Systematic Overview of Radiation Therapy Effects in Hodgkin's Lymphoma

A systematic review of radiation therapy trials in several tumour types was carried out by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for Hodgkin's lymphoma (HL) is based on data from 12 randomized trials and 2 meta-analyses. Data from 3 prospective studies, 29 retrospective studies and 58 other articles were also used. In total, 58 scientific articles are included, involving 27 280 patients. The results were compared with those of a similar overview from 1996 including 38 362 patients. The conclusions reached can be summarized thus: <list id="l1" type="5"> <item>Solid scientific documentation shows that in patients with HL more than 80% in the early stages and 60-70% of younger patients in advanced stages of disease are now cured by the development of radiotherapy and combination chemotherapy.</item><item>Long-term follow-up shows that after 15 to 20 years the mortality from HL in early and intermediate stages is exceeded by other causes of death, mostly secondary malignancies and cardiac deaths, especially myocardial infarction.</item><item>Convincing data show that radiotherapy plays a major role in the development of solid cancers and cardiovascular disease, but no randomized trials have been performed.</item><item>During the past decade increasing awareness of fatal long-term sequelae has fundamentally changed treatment strategies in early and intermediate stages. A thorough long-term follow-up is essential to evaluate the effects of the modifications of the therapy.</item><item>In early stages of disease extended field irradiation is now replaced by short periods of chemotherapy followed by limited radiotherapy to decrease late sequelae. This approach is strongly supported by early reports from randomized trials. Final results cannot be fully evaluated for many years.</item><item>The optimal radiation dose and volume after chemotherapy are not defined or if irradiation is needed at all. Several studies are under way.</item><item>In intermediate stages two recently reported randomized trials indicate that combined modality therapy is preferable and that involved field could replace extended field irradiation. It is still too early to draw any firm conclusions.</item><item>In advanced stages, there is no evidence of any survival benefit from additional radiotherapy.</item><item>The role of radiotherapy in the case of residual tumour and bulky disease still remains controversial.</item><item>There is no scientific support for improved survival with radiotherapy in conjunction with high-dose chemotherapy with stem-cell support.</item><item>Radiotherapy as salvage treatment might be an alternative in late limited nodal recurrence after initial chemotherapy. However, the body of knowledge is small.</item><item>The role of radiotherapy in the treatment of HL is decreasing.</item></list>

New chemotherapy approaches in colorectal cancer.

Colorectal cancer is one of the leading causes of cancer deaths in the Western world, with approximately 50% of all patients dying from metastatic disease. Until recently, therapeutic options for advanced colorectal cancer were mainly confined to chemotherapy with 5-fluorouracil in various schedules, with or without biochemical modulation with leucovorin. The development of new cytotoxic drugs with substantial activity in this tumor during the past 2 years has dramatically changed treatment strategies and therapeutic goals in metastatic colorectal cancer and has introduced neoadjuvant chemotherapy followed by secondary surgery with the intent of long-term survival. Among these new drugs, oral fluoropyrimidines (tegafur/uracil and capecitabine), irinotecan, and oxaliplatin have already established themselves as part of various treatment approaches. Other novel therapeutics including agents designed to act on molecular targets already show promising activity and will become part of combination protocols with current standard chemotherapy.

FDA approval of Antiretroviral Agents: An Evolving Paradigm

The approach to traditional approval of antiretroviral agents in the United States has recently evolved. As in the past, companies can provide confirmatory clinical endpoint data following accelerated approval; alternatively, they can base their claim of efficacy primarily on data demonstrating a sustained reduction in plasma HIV-1 RNA. This change was fueled by issues associated with conducting long-term clinical endpoint trials given the rapidly changing treatment strategies for HIV and the availability of potent combination regimens. The Food and Drug Administration (FDA) hopes that this new approach will help direct more resources to ambitious, collaborative clinical trials. The rapid evolution of traditional approval also illustrates the importance of close collaboration between industry, academia, and the FDA. This field would not have moved forward so rapidly without consensus initiatives such as the Surrogate Marker Collaborative Group, which provided evidence suggesting that a virologic response, in terms of changes in HIV-1 RNA, is a strong predictor of clinical benefit.

The heart failure pandemic: changing patterns, costs, and treatment strategies.

Heart failure is the most important public health problem in cardiovascular medicine, and is increasing in both prevalence and expense. Programs that use an interdisciplinary team to improve outpatient treatment and prevent hospitalizations will help improve care and control costs. But the most important long-term strategy for dealing with the heart failure pandemic is more aggressive primary and secondary prevention.

Surrogate Endpoints in Aids Drug Development: Current Status

During the past several years, significant efforts have been devoted to searching for surrogate endpoints to evaluate AIDS treatments. Efforts were made in the form of research sponsored by the government and trials conducted by the pharmaceutical industry. Rapidly changing treatment strategies, low incidences of clinical endpoints due to prophylactic drug usage for AIDS-defining illness, and poor patient compliance have made long-term large trials to evaluate the clinical benefits of AIDS drugs impossible. The latter has intensified the need for surrogate endpoints. This paper shares with readers activities that have taken place in the search process and what medical, statistical, regulatory, and patient advocacy groups as a whole have accomplished so far. Some results from the collaborative effort to validate CD4 count and HIV-1 viral load as surrogates for the clinical endpoints will be presented using data from AIDS clinical trials. The ultimate question this paper seeks to answer is: Are researchers ...