Tumor-related Symptoms Research Articles

Quality of life after stereotactic radiotherapy for meningioma: a prospective non-randomized study

Stereotactic radiotherapy (SRT) is well-established in the treatment of meningiomas offering high local control with low toxicity. However, the impact of SRT on quality of life (QoL) of patients remains largely unknown. This work aimed to prospectively evaluate QoL (longitudinal analysis) during and after SRT of meningiomas. We performed a single center, one-armed, prospective non-randomized study to assess QoL before and at the end of SRT (median fraction dose: 1.8 Gy; median cumulative dose: 54.0 Gy) and furthermore biannually until 24 months after SRT with the "medical outcome study short form 36". This questionnaire evaluates 8 health parameters summarized in "physical component scale" (PCS) and "mental component scale" (MCS). Between 2005 and 2007, 67 patients were enrolled and treated with SRT. 42/52 patients underwent previous operations and 10/52 primary SRT. Complete follow-up data were available from 44 patients. Compared to the german normal population (GNP) a general decrease in the mean values of all parameters was observed. After SRT mean values still declined and 12 months after SRT all parameters normalized towards their initial values. The cohort (previous operations) had better values for MCS (p = 0.004). The cohort (primary SRT) had worse values for PCS that increased asymptotically 6 months after SRT to values of cohort (previous operations) (p = 0.054). Gender, age and tumor related symptoms did not affect QoL according to MCS and PCS (p > 0.05). Local control was 98 %. Treatment was well tolerated and no severe side effects were observed. Patients with meningiomas have an impaired QoL compared to GNP. The QoL assessment after SRT revealed three phases: "depressive phase", "recovery phase" and "normalization phase". Patients treated with primary SRT developed a stable increase of the mean values for PCS. Gender, age, applied dose, symptomatology did not affect QoL.

Survival impact of surgical resection of primary tumor (SRPT) in metastatic colorectal cancer (mCRC): A population-based cohort study.

456 Background: Currently there is very low quality evidence available regarding survival benefit of SRPT in patients with mCRC. In the absence of randomization the reported benefit may reflect selection of younger and healthier patients with good performance status (PS). We have undertaken a retrospective cohort study to determine the survival benefit of SRPT in mCRC. Methods: A cohort of 1,378 patients with mCRC diagnosed between 1992-2005 in the province of Saskatchewan was evaluated. Kaplan-Meier curves were used to determine survival. Log-Rank test was done to compare survival between the two groups. Cox regression model was used to adjust survival for important prognostic variables. Results: Median age was 70 yrs (22-98) and M:F was 57:43. 27% had ECOG PS of >1 and 62% had a comorbid illness. 944 (69%) patients underwent SRPT. Among 1,378 patients, 40% were operated for tumor related symptoms (33% obstruction, 6% perforation, and 4% heavy bleeding, mutually nonexclusive). Median follow up time for whole cohort was 7.1 months (inter-quartile range 2.5-17.5). 42.3% received chemotherapy and 19.1% received 2nd generation therapy. Median survival of patients who received chemotherapy was 15.9 months. Patients who underwent SRPT had median overall survival of 18.3 months vs. 8.4 months if they did not have surgery (p<0.0001).On multivariate analysis 5FU-based chemotherapy (HR 0.53; 95%CI: 0.45-0.61), metastesectomy (HR 0.54; 95%CI: 0.45-0.64), SRPT (HR 0.55; 95%CI: 0.48-0.62), and 2nd generation chemotherapy (HR 0.65; 95%CI: 0.54-0.77) were correlated with a better survival whereas, elevated CEA level (1.56; 95%CI: 1.30-1.90), leukocytosis (HR 1.54; 95%CI: 1.33-1.80), ECOG PS >1 (HR 1.48; 95%CI: 1.30-1.69), low albumin (HR 1.44; 95%CI: 1.26-1.64), age ≥ 65 yrs (HR 1.21; 95%CI: 1.10-1.38), anemia (HR 1.16; 95%CI: 1.03-1.31), and symptomatic disease (HR 1.12; 95%CI: 1.0-1.26) were correlated with poor survival. Comorbid illness, smoking, and gender did not correlate with survival. Conclusions: This is the first large cohort study that reveals that SRPT in patients with mCRC improves survival independent of chemotherapy, age, functional status and comorbid illness.

Oesophageal cancer—an overview

Oesophageal carcinoma is one of the most virulent malignant diseases and a major cause of cancer-related deaths worldwide. Diagnosis and accuracy of pretreatment staging have substantially improved throughout the past three decades. Therapy is challenging and the optimal approach is still debated. Oesophagectomy is considered to be the procedure of choice in patients with operable oesophageal cancer. Endoscopic measures and limited surgical procedures provide an alternative in patients with early carcinomas confined to the oesophageal mucosa. Chemotherapy and radiotherapy or concurrent chemoradiotherapy are also frequently applied, either as definitive treatment or as neoadjuvant therapy within multimodal approaches. The question of whether multimodal treatment offers improved results has been the focus of many studies since the 1990s. Although results are discordant and even some meta-analyses remain inconclusive, it is now widely accepted that multimodal therapy leads to a modest survival benefit. The role of minimally invasive oesophagectomy is not yet defined. Endoscopic stent insertion, radiotherapy and other palliative measures provide relief of tumour-related symptoms in advanced, unresectable tumour stages.

Future Directions in Metastatic Castration Resistant Prostate Cancer (mCRPC): Clinical Rationale and Use of New-Generation Hormonal Therapies

Several recent studies in mCRPC have identified the mechanisms of tumoral growth after the disease becomes unresponsive to standard hormonal therapy. These studies have highlighted the importance of residual intratumoral androgens in maintaining androgen receptor (AR) transcriptional activity in mCRPC [1]. Based on this findings, it has been possible to develop drugs, blocking the key enzyme in the biosynthesis of androgens through the inhibition of cytochrome p450 17 (CYP17) such as Abiraterone Acetate (AA) and drugs which directly target the AR including Enzalutamide (E) and Orteronel. Before this new knowledge, mCRPC treatment benefited from chemotherapy with taxanes. Recently a new taxane, Cabazitaxel (C), was approved in second line setting in association with prednisone. Retrospective analyses have tried to clarify the current role of chemotherapy in mCRPC patients and the right chemotherapy sequence of use of chemotherapy compared to new hormonal agents. Moreover, it would be important to address changes in the endpoints used in clinical trials, based on the stage of disease including the presence tumor-related symptoms, in order to identify the right therapeutic strategy.

Eribulin monotherapy in a patient with heavily pretreated metastatic breast cancer: Case study and review of the literature

Treatment of heavily pretreated patients with metastatic breast cancer is challenging due to the combination of progressive disease and limited treatment options. Because breast cancer in this setting is not curable, treatment goals include improving/maintaining quality of life, reducing tumor-related symptoms, and prolonging survival. We report on a 42-year-old Hispanic woman with invasive ductal carcinoma (T4 N1 M1), positive for estrogen and progesterone receptors and negative for HER2. She had been heavily pretreated with radiation (to bone metastases), hormonal therapy, and multiple systemic therapies—including a nanoparticle albumin-bound paclitaxel/bevacizumab/gemcitabine combination and pegylated liposomal doxorubicin. Because of toxicity or disease progression, none of these treatments was used for more than 4 months. After receiving eribulin (in a clinical trial), the patient remained in stable disease for 21 months and generally tolerated eribulin well. (Thrombocytopenia with resulting gastrointestinal bleeding occurred but was resolved with a dose reduction.) The case is discussed in the context of current treatment goals and modalities in the setting of late-line metastatic breast cancer. Treatment options include newer chemotherapeutic agents such as eribulin, a recently approved non-taxane microtubule dynamics inhibitor whose mechanism of action differs from that of other tubulin-targeting agents.

Prostate cancer incidence and newly diagnosed patient profile in Spain in 2010

What's known on the subject? and What does the study add? Prostate cancer (PCa) accounts for 12% of newly diagnosed cases of cancer in Europe. It is one of the most frequently diagnosed tumours in the developed world. Since the introduction of prostate specific antigen as a test for early detection of PCa, the rate of diagnosis has increased significantly and specific mortality has reduced in most western countries. Most of the data on the incidence of PCa are obtained from population-based cancer registries which frequently do not cover the whole population. This first national hospital-based PCa registry aims not only to estimate the incidence of the disease but to ascertain the clinical profile of newly diagnosed PCa patients, a useful tool for evaluating the impact of the disease and its socio-health management. • To estimate the 2010 incidence of prostate cancer (PCa) in Spain. • To describe the clinical profile of newly diagnosed cases using a nationwide hospital-based registry. • This was a national epidemiological observational study in 25 public hospitals with a specific reference population according to the National Health System. • Sociodemographic and clinical variables of all newly diagnosed, histopathologically confirmed PCa cases were collected in 2010, in the area of influence of each centre. Cases diagnosed in private practice were not collected (estimated nearly 10% in Spain). • Data monitoring was external to guarantee quality and homogeneity. • The age-standardized PCa incidence was determined based on the age distribution of the European standard population. • In all, 4087 new cases of PCa were diagnosed for a reference population of 4933940 men (21.8% of the Spanish male population). • The estimated age-standardized PCa incidence was 70.75 cases per 100000 men. • Mean age at diagnosis was 69 years; 11.6% of patients presented with tumour-related symptoms and 39.5% with LUTS. Median PSA was 8 ng/mL. Gleason score was ≤ 6 in 56.5%, 7 in 26.7% and >7 in 16.8% of patients. At diagnosis, 89.8% had localized, 6.4% locally advanced and 3.8% metastatic disease. • This study on PCa incidence in Spain, a western country with intensive opportunistic PSA screening, shows that PCa is a high incidence tumour, diagnosed close to 70 years, usually asymptomatic. • Almost 40% of cases have low risk disease with a risk of over-diagnosis and over-treatment. • Around 55% of patients with intermediate or high risk disease are candidates for active therapy which may result in a reduction of cancer-specific mortality.

Editorial Comment

Although generally effective in suppressing serum androgens, gonadotropin-releasing hormone (GnRH) agonists have several liabilities that have motivated the development of alternatives. Before reducing testosterone, GnRH agonists such as leuprolide initially produce a surge in luteinizing hormone (LH), which consequently induces a transient rise in serum testosterone, an event that can result in worsening tumor-related symptoms termed a clinical flare in men with metastatic disease. Microsurges in testosterone commonly occur with repeat GnRH agonist dosing, and breakthrough rises in serum testosterone exceeding castrate levels during treatment occur in up to 13% of men.

Reply

We appreciate the thoughtful Editorial Comment on our manuscript “The Effect of Baseline Testosterone on the Efficacy of Degarelix and Leuprolide: Further Insights from a 12-Month, Comparative, Phase III Study in Prostate Cancer Patients.” We agree that testosterone levels required after gonadotropin-releasing hormone (GnRH) manipulation merit reevaluation, especially with the availability of improved measurement techniques. Although there is currently a lack of consensus on the optimum suppressed testosterone level in prostate cancer (PCa), a 0.2 ng/mL threshold has been recommended after androgen deprivation therapy (ADT) in advanced disease. 1 Djavan B. Eastham J. Gomella L. et al. Testosterone in prostate cancer: the Bethesda consensus. BJU Int. 2011; (In press) Google Scholar Editorial CommentUrologyVol. 80Issue 1PreviewAlthough generally effective in suppressing serum androgens, gonadotropin-releasing hormone (GnRH) agonists have several liabilities that have motivated the development of alternatives. Before reducing testosterone, GnRH agonists such as leuprolide initially produce a surge in luteinizing hormone (LH), which consequently induces a transient rise in serum testosterone, an event that can result in worsening tumor-related symptoms termed a clinical flare in men with metastatic disease. Microsurges in testosterone commonly occur with repeat GnRH agonist dosing, and breakthrough rises in serum testosterone exceeding castrate levels during treatment occur in up to 13% of men. Full-Text PDF

The trans-sphenoidal resection of pituitary adenomas in elderly patients and surgical risk

In western countries, the process of "ageing of the population" is increasingly forcing clinical medicine to find answers for pathologies affecting the elder segments of our community. In this respect, pituitary adenomas often raise difficult questions on surgical indications, since little is known about postoperative morbidity and mortality in elderly patients. The transsphenoidal endonasal approach (TNS), which is considered the gold standard for surgical resection of the majority of functioning and non-functioning pituitary adenomas, is supposed to be a low morbidity and mortality procedure in adult patients. However, only a few contradicting data are available in the literature about elderly patients. In this paper we retrospectively analyze a cohort of 43 consecutive patients aged more than 65years, operated on for pituitary adenomas at our Institution in the years 1998-2007. These patients were treated by transsphenoidal endonasal approach (TNS) for resection of non-functioning pituitary adenomas (n=31), GH-secreting adenomas (n=4) and ACTH-secreting adenomas (n=8). Clinical records reported a macroadenoma with tumour-related mass symptoms in about 80% of patients; single or multiple pituitary deficits were present in 44% of patients. Regarding comorbidities, cardiac disease was the most frequently observed (86%); assessment of anaesthesiological risk indicated a moderate to severe ASA score in most patients, 11% showing a 4-5 score. On the basis of current criteria, our retrospective analysis revealed that cure was achieved in 54% of patients. The outcome was similar to that observed in the general population of patients undergoing transphenoidal surgery in our centre, without differences in the rate of surgical and endocrinological cure, minor and major surgical complications and hospitalization duration. In particular, no significant anaesthesiological complications were observed and no patient developed either permanent diabetes insipidus or cerebrospinal fluid rhinorrhea. In conclusion, in specialized centres the surgical treatment of pituitary adenomas via the transsphenoidal route can be a safe and effective procedure even in elderly patients.

Resection of the primary tumour versus no resection prior to systemic therapy in patients with colon cancer and synchronous unresectable metastases (UICC stage IV): SYNCHRONOUS - a randomised controlled multicentre trial (ISRCTN30964555)

BackgroundCurrently, it remains unclear, if patients with colon cancer and synchronous unresectable metastases who present without severe symptoms should undergo resection of the primary tumour prior to systemic chemotherapy. Resection of the primary tumour may be associated with significant morbidity and delays the beginning of chemotherapy. However, it may prevent local symptoms and may, moreover, prolong survival as has been demonstrated in patients with metastatic renal cell carcinoma. It is the aim of the present randomised controlled trial to evaluate the efficacy of primary tumour resection prior to systemic chemotherapy to prolong survival in patients with newly diagnosed colon cancer who are not amenable to curative therapy.Methods/designThe SYNCHRONOUS trial is a multicentre, randomised, controlled, superiority trial with a two-group parallel design. Colon cancer patients with synchronous unresectable metastases are eligible for inclusion. Exclusion criteria are primary tumour-related symptoms, inability to tolerate surgery and/or systemic chemotherapy and history of another primary cancer. Resection of the primary tumour as well as systemic chemotherapy is provided according to the standards of the participating institution. The primary endpoint is overall survival that is assessed with a minimum follow-up of 36 months. Furthermore, it is the objective of the trial to assess the safety of both treatment strategies as well as quality of life.DiscussionThe SYNCHRONOUS trial is a multicentre, randomised, controlled trial to assess the efficacy and safety of primary tumour resection before beginning of systemic chemotherapy in patients with metastatic colon cancer not amenable to curative therapy.Trial registrationISRCTN30964555

Incidental Detection of Pancreatic Neuroendocrine Tumors: An Analysis of Incidence and Outcomes

Pancreatic neuroendocrine tumors (NETs) are increasingly discovered incidentally during radiologic or endoscopic examinations. The frequency of incidental detection is unknown. It is also unclear whether patients with incidentally discovered, early-stage, asymptomatic tumors should be treated similarly to patients who present with tumor-related symptoms. Patients with nonmetastatic pancreatic NETs treated at the H. Lee Moffitt Cancer Center between 1999 and 2010 were assigned a stage (I-III) on the basis of the new American Joint Committee on Cancer classification. The frequency of incidentally diagnosed tumors was evaluated and stratified by stage. Progression-free survival was measured by log rank testing to compare patients with incidentally detected versus symptomatic tumors. Multivariate analysis was performed controlling for other prognostic factors including tumor stage, grade, and location, and patient age. Among 143 patients with nonmetastatic pancreatic NETs, 56 patients (40%) had tumors that were discovered incidentally. Most stage I tumors (55%) were incidental. The 5-year progression-free survival rate was 86% for incidentally diagnosed tumors, versus 59% for symptomatic tumors (P = 0.007). On multivariate analysis, incidental detection of tumors was the strongest prognostic factor for progression. A sizable fraction of patients with early-stage pancreatic NETs are diagnosed incidentally during evaluations for other conditions or unrelated symptoms. This study highlights the necessity of developing guidelines for management of patients with incidentally discovered early-stage tumors.

Gemcitabine chemotherapy until symptomatic disease progression in advanced pancreatic cancer: A retrospective analysis.

372 Background: Gemcitabine was established as the standard first-line therapy for patients with advanced pancreatic cancer in 1997 after a randomized phase III study showed a statistically significant improvement in clinical benefit response and a modest improvement in median survival time, compared to bolus 5FU chemotherapy. The natural history of advanced pancreatic cancer is characterised by the rapid and relentless progression of tumor-related symptoms, thus we have analysed the outcome of our patients with advanced pancreatic cancer who have been treated with gemcitabine until symptomatic disease progression, without the use of regular radiological assessment. Methods: A retrospective analysis was conducted on all patients with advanced pancreatic cancer who were treated with first-line gemcitabine chemotherapy between January 2008 – December 2009. Results: A total of 50 patients were identified (21 with locally advanced disease, 29 with metastatic disease). The overall median survival was 10.4 months (11.3 months for patients with locally advanced disease, 7.2 months for patients with metastatic disease). Conclusions: Our single centre experience suggests that clinical decision-making based on symptomatic disease progression in advanced pancreatic cancer, results in survival outcomes that are comparable to published trial data.

PC-FACS

PC-FACS

Stereotactic Radiosurgery for Recurrent or Unresectable Pilocytic Astrocytoma

To report the outcomes in patients with recurrent or unresectable pilocytic astrocytoma (PA) treated with Gamma Knife stereotactic radiosurgery (SRS). Retrospective review of 18 patients (20 lesions) with biopsy-confirmed PA having SRS at our institution from 1992 through 2005. The median patient age at SRS was 23 years (range, 4-56). Thirteen patients (72%) had undergone one or more previous surgical resections, and 10 (56%) had previously received external-beam radiation therapy (EBRT). The median SRS treatment volume was 9.1 cm(3) (range, 0.7-26.7). The median tumor margin dose was 15 Gy (range, 12-20). The median follow-up was 8.0 years (range, 0.5-15). Overall survival at 1, 5, and 10 years after SRS was 94%, 71%, and 71%, respectively. Tumor progression (local solid progression, n = 4; local solid progression + distant, n = 1; distant, n = 2; cyst development/progression, n = 4) was noted in 11 patients (61%). Progression-free survival at 1, 5, and 10 years was 65%, 41%, and 17%, respectively. Prior EBRT was associated with inferior overall survival (5-year risk, 100% vs. 50%, p = 0.03) and progression-free survival (5-year risk, 71% vs. 20%, p = 0.008). Nine of 11 patients with tumor-related symptoms improved after SRS. Symptomatic edema after SRS occurred in 8 patients (44%), which resolved with short-term corticosteroid therapy in the majority of those without early disease progression. SRS has low permanent radiation-related morbidity and durable local tumor control, making it a meaningful treatment option for patients with recurrent or unresectable PA in whom surgery and/or EBRT has failed.

Chairperson's introduction

Despite significant advances in the diagnosis and treatment of breast cancer, approximately one third of patients still develop, and subsequently die from metastatic breast disease. Globally, half a million deaths each year are attributable to metastatic breast cancer, and the median survival time from diagnosis of secondary disease is approximately three years. The range is very wide, however, with some patients having more indolent disease living for 10−15 years in some cases, whilst in others survival from diagnosis of metastatic disease can be only a matter of months. In part this reflects the biological diversity of the disease, with some women who have oestrogen receptor (ER)positive tumours that show extreme sensitivity to hormonal treatments, while in others with so-called triple-negative breast cancer the secondary sites of disease can display relative resistance to all therapies. In addition, the disease may be manifest as different patterns of metastatic spread, ranging from limited bone metastases to widespread and life-threatening metastases in visceral organs such as the liver, lung and brain. Both of these factors will influence the broad range of expected survival for an individual patient. While recent years have witnessed substantial developments in various therapies that have improved the outlook for many women with breast cancer, the fact remains that at present secondary breast cancer cannot be cured. As such, the socioeconomic and psychological impact of the condition and its management is a major health problem for various reasons. The high prevalence of the disease, together with the relatively long natural history for many patients, means that in the UK approximately 100,000 women are living with a diagnosis of secondary breast cancer each year. However, for these women the true impact of living with an incurable condition and coping with an uncertain future is something that often goes unrecognised by health care professionals. The diagnosis of metastatic breast cancer is always a devastating event for any patient who has received previous therapy for early breast cancer that was given with the hope and expectation of cure. Therefore, when secondary disease returns this is associated with the realisation that “cure” is no longer possible, and that by and large one day most women will die from their disease. So the question that every patient inevitably asks when faced with this scenario is “how long do I have to live?” This is not a question that can be readily answered at the point of diagnosis of metastatic disease, as many factors will influence subsequent survival, including sites and distribution of secondary disease, the biological subtype of breast cancer, host comorbidities and organ function, and most importantly the response of the metastatic breast cancer to the individual therapies. When treating metastatic breast cancer, however, the primary aim is to palliate diseaserelated symptoms and maintain quality of life. This is achieved by utilising systemic anti-cancer therapies such as endocrine therapy, biological approaches and chemotherapy, and also loco-regional therapies such as radiotherapy and surgery in certain circumstances. Each of these therapies can impact on tumour growth, thus relieving tumour-related symptoms and inducing disease control due to some form of partial remission. Indeed, it is well recognised that quality of life in advanced breast cancer is clearly linked to the likelihood of treatment response. While metastatic breast cancer cannot be cured, modern systemic and loco-regional treatment can be very effective in maximising a patient’s duration of quality time without disease-related symptoms, which, if significant in itself, will often be manifest as prolonged survival. In this setting it is always important that this gain in quality time and life expectancy is achieved without any significant treatment-related toxicities. With the introduction of more effective therapies over the last two decades, there have been substantial improvements in clinical outcomes for women with metastatic breast cancer compared with 30 years ago. Indeed, many patients can now expect to live with metastatic secondary breast cancer for several years. However, many challenges remain in the development

Outcome and Natural History of Patients with Stage IV Colorectal Cancer Receiving Chemotherapy Without Primary Tumor Resection

There is a trend toward nonsurgical management of patients with nonobstructing metastatic (stage IV) colorectal cancer (CRC), although some will eventually undergo surgery. We examined patients with metastatic CRC who were managed with an intact primary tumor. An institutional review board (IRB)-approved database was retrospectively reviewed. All patients presenting with stage IV CRC from 2000 to 2008 were identified and analyzed. Among the 255 patients identified, 112 were taken directly to the operating room for either primary tumor resection or colostomy/bypass. Among the remaining 143 patients, 97 were managed without developing primary tumor-related symptoms, and 14 (9.8%) developed significant primary tumor-related symptoms necessitating operative or endoscopic management. Of the patients who developed symptoms, oxaliplatin and/or irinotecan was used among 71.4% of patients, and bevacizumab in 50%. Forty-two patients in the series underwent elective primary tumor resection after receiving chemotherapy. No independent predictors for development of primary tumor-related symptoms could be identified after controlling for age, gender, tumor location, number of metastatic sites, and type of chemotherapy. Median overall survival was 34 months for those who underwent elective primary tumor resection after chemotherapy, and 16 months for those who failed chemotherapy and developed symptoms. Among patients with metastatic CRC without an initial indication for surgery, incidence of obstruction or perforation after initiating chemotherapy was low (9.8%). No predictors of primary tumor-related complications could be identified. Survival was favorable among the highly selected cohort of patients who underwent elective primary tumor resection after chemotherapy.

A specific approach for elderly patients with head and neck cancer

Approximately 10% of head and neck (HN) tumors occur in patients aged more than or equal to 80 years. In this population, the main challenge for physicians is to deal with the benefit/risk ratio of treatments and tumor-related symptoms. As elderly patients are generally excluded from clinical trials, there is a lack of evidence-based data with regard to the most appropriate multidisciplinary management. The prevalence of frailty and the pattern of comorbidities in this specific population are still unknown. The management of these tumors in a geriatric context is complex due to the high risk of toxicity of locoregional treatments. Thus, physicians often have to adapt to the treatment schedule to decrease potential adverse effects even with a risk of undertreatment. A retrospective series reported that the treatment delivered to elderly patients presenting with HN tumor complies with an institution's policy in less than 50% of cases, emphasizing the need to assess the outcome of personalized/adapted treatment in geriatric patients. The major issue is to determine which adaptation could be carried out, and then, what could be the respective individual benefit/risk ratio of each adaptation. In this review, we will focus on the locoregional management of elderly patients, and develop the issue of adapted local treatment. We will discuss the feasibility of adapted surgery and radiotherapy and provide current evidence-based data that may allow physicians involved in locoregional treatment of elderly patients with HN cancers to be acquainted with practical guidelines. Then, we will highlight the importance of nutritional support in this population in which the prevalence of malnutrition is high.

Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer – A randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO)

BackgroundThe value of second-line therapy for metastatic gastric cancer is unclear. So far there are no randomised phase III data comparing second-line chemotherapy to best supportive care (BSC). In this prospective, multicenter, open label, randomised phase III study we compared irinotecan to BSC to evaluate the impact on survival of second-line chemotherapy. MethodsEligible patients (pts) had metastatic or locally advanced gastro-oesophageal junction or gastric adenocarcinoma, objective tumour progression during or within 6months after first-line chemotherapy and ECOG performance status 0–2. Stratification for time of progression after first-line therapy, ECOG PS and pretreatment secured even distribution of important prognostic factors. TreatmentArm A: Irinotecan 250mg/m2q3w (first cycle) to be increased to 350mg/m2, depending on toxicity. Arm B: BSC. FindingsBetween 10/2002 and 12/2006 40 pts were randomised. The study was closed prematurely due to poor accrual. Responsefor arm A (19 pts evaluable): No objective responses, SD 53%, PD 47%. Improvement of tumour related symptoms: Arm A 50% of pts, arm B 7%. Overall Survival: (all events in 40 pts have occurred): The hazard ratio for death was reduced to 0.48 (95%CI 0.25–0.92) in the irinotecan-arm (p=0.012). Median survival arm A: 4.0months (95% CI 3.6–7.5), arm B: 2.4months (95% CI 1.7–4.9). InterpretationIrinotecan as second-line chemotherapy significantly prolongs overall survival compared to BSC in the studied pts. Second-line chemotherapy can now be considered as a proven treatment option for metastatic or locally advanced gastric cancer. FundingThe study was supported by a research grant from Aventis and Pfizer.

Stage IA Ovarian Cancers

The purpose of this study was to compare sonographic findings and histopathologic types of stage IA ovarian cancers between groups with normal and elevated cancer antigen 125 (CA-125) levels. Between 2000 and 2009, 146 stage IA ovarian cancers were treated surgically (85 invasive and 61 borderline, 73 self-referred with tumor-related symptoms, 20 self-referred with nonspecific symptoms, 52 identified through screening, and 1 other). Of these, 87 cases (60%) had normal serum CA-125 levels (<35 U/mL). Their pre-operative sonographic findings and histopathologic types were compared to those of cases with elevated CA-125 levels. Statistically significant differences were found between the proportions of patients with elevated CA-125 levels in groups having tumors with maximal diameters of less than 20 cm and at least 20 cm (P = .03) and groups having tumors with less than 50% and 50% to 80% solid components (P = .02). In the group with normal CA-125 levels, we found predominantly mucinous adenocarcinoma in multilocular cysts with less than 50% solid components (25 cases), and clear cell adenocarcinoma in unilocular cysts with less than 50% solid components (12 cases), whereas in the group with elevated CA-125 levels, mucinous adenocarcinoma in multilocular cysts with less than 50% solid components (19 cases) and endometrioid adenocarcinoma in solid tumors (≥80% solid components) were predominant (5 cases). Stage IA ovarian cancers with normal CA-125 levels tend to be smaller, have less solid components, and have a slightly different distribution of histopathologic types than cancers with elevated CA-125 levels.

Chemotherapy Definitions and Policies for Thymic Malignancies

Thymic malignancies are rare epithelial tumors that may be aggressive and difficult to treat.1 Thymomas are usually localized to the anterior mediastinum and are frequently eligible for upfront surgical resection, which is the mainstay of the curative-intent treatment.1 However, approximately 30% of patients present with an advanced tumor at the time of diagnosis, with invasion of neighboring organs, dissemination to the pleura, the pericardium, or less frequently extrathoracic organs. In such cases, chemotherapy has been used both to reduce the tumor burden—possibly allowing subsequent surgery or radiotherapy—and to achieve prolonged disease control. Recurrence after resection may be similarly treated with chemotherapy. Thymic carcinomas, although rare, are usually already advanced at the time of presentation, and systemic therapy is important for almost all of these patients. Knowledge regarding chemotherapy for thymic tumors has mainly been based on retrospective series,2–9 although several prospective trials have also been conducted.10–21 These studies have clearly demonstrated the chemosensitivity of thymoma, and to a lesser extent thymic carcinoma, to various cytotoxic agents and combinations. However, details of patient selection are often lacking (either disease extent or general condition), and the intent of the treatment sequence is often vague. Adoption of a common language and definition of terms is crucial for the International Thymic Malignancies Interest Group (ITMIG) effort to develop a international prospective database of thymic tumors. The article by Huang et al.22 provides definitions for survival and endpoints for recurrences assessment and discusses how to measure response to treatment. Herein, we discuss additional points with regard to chemotherapy, including treatment sequence, general modalities, and impact of corticosteroids.