A little to a lot or a lot to a little: is NTCP always minimized in multiport therapy?

Purpose: We address the question of whether or not, for the same average (or integral) dose, a smaller uniform dose to an entire normal tissue structure always results in a lower normal tissue complication probability (NTCP) than does a proportionally larger dose to a partial volume of the same structure.Methods and Materials: A recent compilation of NTCP data and two theoretical formulations of the dependence of NTCP on dose and partial volume irradiated—the Lyman probit equation and the binomial model—are used to examine this question. Both models fit equally well available NTCP data.Results: Empirical data indicate that for lung, kidney, and possibly liver (but not for esophagus, brain, or heart), given a fixed tumor dose and fixed integral dose, NTCP can be minimized by irradiating a partial volume fraction rather than the entire normal organ. The binomial model supports this interpretation, whereas the probit model predicts that for all organs uniform irradiation of the whole organ always results in the lowest possible NTCP.Conclusions: In contrast to what is commonly believed, this study suggests that for at least two normal tissues, namely lung and kidney, there may be situations where “a lot to a little” (i.e., fewer treatment ports) will result in higher tumor control probability and better treatment plan than “a little to a lot” (i.e., multifield treatment). This finding, which is independent of the binomial or probit models used here, depends only on the accuracy of the empirical NTCP data. It is also interesting to note that: a) lung and kidney are commonly classified as parallel tissues, while the others have more of a serial architecture; and b) the choice of the NTCP model can have a profound impact on treatment planning decisions.     

How to be a patient in a palliative life experience? A qualitative study to enhance knowledge about coping abilities in advanced cancer patients

To date there has been little research that reveals and describes the connection between the individual and his or her environment, which is the foundation for the coping process. These findings are part of a grounded theory study. The article shows how "the struggle to be a participant in one's own life" was identified as a central tendency in coping with advanced cancer. It involved a pattern of four life conditions: alleviation from a life-threatening illness, carry on a normal life, live with powerlessness, and find courage and strength, which were characterized by a series of limitations and resources significant to coping.     

Do beta-tubulin mutations have a role in resistance to chemotherapy?

beta-tubulin is the target of various antitubulin agents used in the treatment of cancer. After beta tubulin was shown to confer resistance to antitubulin agents in established cell lines, several studies have investigated the DNA sequence of this compound in clinical samples. However, these findings are highly controversial, since sequencing experiments showed that the original clinical observation of mutations in the gene resulted from inclusion of non-functional beta-tubulin pseudogenes. At least nine such pseudogenes are known, and all share substantial sequence homology with the functional gene. Subsequent studies have concluded that beta-tubulin mutations in clinical samples are rare, and unlikely to contribute to drug resistance. Here, we overview the beta-tubulin gene family and summarise the results of studies done comparing beta-tubulin mutations with antitubulin drug resistance.     

Antibodies to 4-hydroxyandrostenedione — a new anti-breast cancer agent suitable for use in a radioimmunoassay

Summary A specific antiserum suitable for radioimmunoassay (RIA) of 4-hydroxy-4-androstene-3,17 dione (4-OHA) has been developed. Sheep antiserum was raised by injecting two different conjugates prepared by coupling 4-OHA to ovalbumin. Antisera obtained from a sheep immunised with 4-hydroxy-testosterone-17-hemisuccinate ovalbumin conjugate were of higher titre and more specific than antisera obtained from sheep immunised with 4-hydroxyandrostenedione-7-carboxyethylthioether. The antiserum bound 50% of 20 picograms of [6,7-³H]-4-OHA at an initial dilution of 1:270. The most relevant steroids, androstenedione (AD) and testosterone (T) were tested and showed cross reactivity of 2.7% and 5.1% respectively. The lower limit of detection was 4.5 pg/tube. Antisera from this animal will prove useful as the basis of a sensitive and specific RIA for clinical pharmacokinetic studies of 4-OHA.     

TRAIL resistance results in cancer progression: a TRAIL to perdition?

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL, APO-2L) is a mediator of cell death that preferentially targets cancer cells. The potential of TRAIL as a chemotherapeutic agent is limited, however, because of the emergence of TRAIL resistance. Furthermore, recent studies have demonstrated that alternative TRAIL signaling is unmasked in TRAIL resistant cells. In these cells, the predominant effect of TRAIL receptor activation is the activation of nuclear factor-kappaB (NF-kappaB), which promotes tumor metastases and invasion. TRAIL resistance can occur at the level of the death inducing signaling complex via upregulation of cFLIP or via an increase in antiapoptotic proteins of the Bcl-2 family. A paradigm emerges from this information, that chemotherapy, targeting NF-kappaB, cFLIP, or antiapoptotic proteins of the Bcl-2 family, in combination with TRAIL maybe more rational than TRAIL therapy alone.     

Is contrast enhancement required to visualize a known breast tumor in a pre-operative CT scan?

Background and purpose

A pre-operative CT scan with contrast enhancement (CE) has recently been proposed to improve tumorbed delineation in breast conserving therapy. However, it is not clear whether CE is required for visualization of a known breast tumor. The main aims of this study were to compare the sensitivity of a CE-CT scan with a native CT scan (i.e. without CE) and to identify characteristics predictive for the requirement of CE.

Patients and methods

Both a CE-CT and a native CT were made in 58 breast cancer patients (age 37–75 yr), prior to breast conserving surgery. Visibility of the tumor on CT was scored by three observers (clearly visible/doubtful/not visible). Age, tumor size, palpable tumor yes/no, histology, and visibility on mammography were analyzed with respect to the visibility of the tumor on the native CT.

Results

The sensitivity for tumor detection was better for CE-CT (95%) than for native CT (83%) (p < 0.001). Only mammographic visibility scores appeared to be significantly correlated with the visibility of the tumor on the native CT (p = 0.013).

Conclusion

In most patients CE is not required to visualize a known breast tumor. Mammographic visibility is a good parameter to decide on the use of CE.     

Health-related quality of life in survivors of tumours of the central nervous system in childhood—a preference-based approach to measurement in a cross-sectional study

There is an evident need to measure the comprehensive burden of morbidity experienced by survivors of brain tumours in childhood. To this end, a questionnaire based on the Health Utilities Index mark 2 (HUI2) and mark 3 (HUI3) systems was completed independently for a cohort of such children by their parents, by a nurse, by physicians and by a selected group of the children themselves. Each of the HUI2 and HUI3 systems consists of a multi-attribute health status classification scheme linked to a preference function which provides utility scores for levels within single attributes (domains of health) and for global health states. All eligible families (n=44) participated. Even cognitively impaired children of at least 9.5 years of age could complete the questionnaire. The greatest burden of morbidity, occurring in two-thirds of children, was in the attribute of cognition. Surprisingly, almost one-third of children experienced pain. Global health status was lowest in children who underwent radiotherapy before the age of 5 years and the corresponding utility scores were related inversely to the volume irradiated. Children with demonstrable disease had lower scores than those in whom disease was not evident. There was a high level of agreement (intraclass correlation coefficients >0.5) on formal assessment of inter-rater reliability for global health-related quality of life utility scores. The usefulness of measures of health status and health-related quality of life, in children surviving brain tumours, has been demonstrated by this study.     

Do the progesterone receptors have a role to play in gallbladder cancer?

Background: Gallstone disease as well as gallbladder cancer are more common in women and female sex hormones may be involved in their etiology. Aim and Methods: To determine whether female sex hormones have a role in the pathogenesis, of gallbladder carcinoma and in its prognosis, we estimated, by enzyme immunoassay, the estrogen and progesterone receptors (ER and PgR) in the gallbladders of 21 patients with gallbladder cancer, 19 patients with cholelithiasis, and 6 patients who underwent incidental removal of essentially normal gallbladder as a component of wider resection. Results: ER were present in the gallbladder mucosa in all the three groups in proportions which were not significantly different (9/21 in carcinoma, 4/19 in gallstones, and 1/6 normal), whereas the expression of PgR was greater in carcinomas (13/18), less in cholelithiasis (4/12), and absent in normal gallbladders. PgR expression was higher in tumors of lower stage (7/7) and lower in advanced disease stage IV tumors (6/11). PgR expression was associated with better disease stage (p=0.05) and significantly longer overall survival (median survival of 301 d vs 54 d) as well as better survival within the same stage (269 d vs 54 d for stage IV disease, p=0.011). Cox’s regression analysis showed that PgR was an independent risk factor (R=0.2283, p=0.0035). Conclusions: Our findings suggest that the female sex hormones may have a role in the pathogenesis of gallbladder cancer and that PgR expression has a prognostic significance. We believe that when this relationship is reaffirmed by larger studies, gallbladder cancer may be treated with appropriate sex hormonal manipulation.     

Is blinding the endoscopists to bowel preparations in randomized-controlled trials a reality?

BACKGROUND: A number of studies compared the quality, efficacy and tolerability of oral sodium phosphate (NaP) and polyethylene glycol (PEG)-based solutions in preparation for colonoscopy. The primary aim of this study was to explore whether endoscopists can be effectively blinded to the type of bowel preparation. METHODS: We recruited 3 experienced endoscopists and 57 outpatients (18-65 years old) undergoing colonoscopy. We randomized eligible patients to receive one of the two bowel preparations. Endoscopists who performed the tests were blinded to the type of preparation, and made their best judgment on the type and quality of the bowel preparation. RESULTS: Forty-five patients completed the study. The overall correct estimation of the type of bowel preparation was 60.0% (95% CI; 45.5%, 73.0%). The cleansing quality did not differ between the two preparations. Patients found oral NaP solution much easier to take (81.8% versus 36.4%; P = 0.005) and the PEG-based group tended to have more nausea or vomiting. 47.6% of patients in the PEG group indicated they would prefer to try another bowel preparation in the future compared to 4.5% in the oral NaP group (P = 0.002). We stopped the study after an interim analysis indicating that more than 600 patients would be required to detect statistically significant differences in the primary aim. CONCLUSION: Our findings suggest that blinding of endoscopists in clinical trials comparing oral NaP to PEG had a relatively low likelihood of bias. The study also suggests that oral NaP is easier to take and more tolerable than PEG without impairing cleansing quality.     

Patients’ willingness to participate in a breast cancer biobank at screening mammogram

To characterize patients’ willingness to donate a biospecimen for future research as part of a breast cancer-related biobank involving a general screening population. We performed a prospective cross-sectional study of 4,217 women aged 21–89 years presenting to our facilities for screening mammogram between December 2010 and October 2011. This HIPAA-compliant study was approved by our institutional review board. We collected data on patients’ interest in and actual donation of a biospecimen, motivators and barriers to donating, demographic information, and personal breast cancer risk factors. A multivariate logistic regression analysis was performed to identify patient-level characteristics associated with an increased likelihood to donate. Mean patient age was 57.8 years (SD 11.1 years). While 66.0 % (2,785/4,217) of patients were willing to donate blood or saliva during their visit, only 56.4 % (2,378/4,217) actually donated. Women with a college education (OR = 1.27, p = 0.003), older age (OR = 1.02, p < 0.001), previous breast biopsy (OR = 1.23, p = 0.012), family history of breast cancer (OR = 1.23, p = 0.004), or a comorbidity (OR = 1.22, p = 0.014) were more likely to donate. Asian-American women were significantly less likely to donate (OR = 0.74, p = 0.005). The major reason for donating was to help all future patients (42.3 %) and the major reason for declining donation was privacy concerns (22.3 %). A large proportion of women participating in a breast cancer screening registry are willing to donate blood or saliva to a biobank. Among minority participants, Asian-American women are less likely to donate and further qualitative research is required to identify novel active recruitment strategies to insure their involvement.     

The right to be forgotten: a change in access to insurance and loans after childhood cancer?

Purpose

Access to insurance for a loan or a mortgage is an important issue for childhood cancer survivors. The aim of this study was to describe difficulties experienced by adult survivors.

Methods

A total of 1920 survivors treated before the age of 18 in five French cancer centers responded to a questionnaire in 2010. Survivors who had tried to obtain a loan were asked if they had experienced difficulties, which were defined as experiencing rejection, higher premiums, or exclusions. The questionnaire investigated health problems related to the circulatory, respiratory, digestive, urinary, endocrine, hormonal, and nervous systems. Second tumors, diabetes mellitus, cardiac disease, and stroke were ascertained from a physician’s report or medical records. Multivariable analyses were conducted to identify the characteristics of survivors reporting difficulties.

Results

Difficulties were experienced by 10.4% of those who had tried to obtain a small loan (n = 787) and by 30.1% of those who had tried to obtain a home loan (n = 909). Disclosure of childhood cancer to the insurer and amputation surgery were negatively associated with insurance accessibility, even when controlling for age, gender, education, health-related unemployment, familial situation, and severe or life-threatening conditions such as cardiovascular diseases, second cancers, or diabetes.

Conclusion

This study showed that the financial burden of cancer can extend decades after diagnosis.

Implications for Cancer Survivors

Thanks to a 2016 law, French cancer survivors no longer have to disclose their cancer to insurers after a fixed number of years. This law will probably lessen the socioeconomic burden of cancer.

     

Is there a cost to poor communication in cancer care?: a critical review of the literature

In this paper, the authors engage in a critical analysis of the existing empirical literature which addresses the impact of ineffective communication between cancer patients and clinicians. It is increasingly accepted that communication plays a significant role in many aspects of the care experience, and that poor communication can have a significantly negative influence on the patient's psychosocial experience, symptom management, treatment decisions, and quality of life. However, scant attention has been given to the idea that poor communication may also have an economic impact worthy of attention. This area has not been the focus of systematic inquiry or substantive critical consideration. On the basis of critical analysis of the limited empirical evidence that exists across a wide range of studies in related areas, the authors propose that the existential and material costs associated with poor communication in cancer care may well be considerable, and conclude with a call to mobilize a heightened enthusiasm for addressing the research challenges in this field.     

Proanthocyanidins and other flavonoids in relation to endometrial cancer risk: a case–control study in Italy

Background:

Because of their antioxidant and antimutagenic properties, flavonoids may reduce cancer risk. Some flavonoids have antiestrogenic effects that can inhibit the growth and proliferation of endometrial cancer cells.

Methods:

In order to examine the relation between dietary flavonoids and endometrial cancer, we analysed data from an Italian case–control study including 454 incident, histologically confirmed endometrial cancers and 908 hospital-based controls. Information was collected through a validated food-frequency questionnaire. We applied data on food and beverage composition to estimate the intake of flavanols, flavanones, flavonols, anthocyanidins, flavones, isoflavones, and proanthocyanidins. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from multiple logistic regression models conditioned on age and study centre and adjusted for major confounding factors.

Results:

Women in the highest quartile category of proanthocyanidins with ⩾3 mers vs the first three quartile categories had an OR for endometrial cancer of 0.66 (95% CI=0.48–0.89). For no other class of flavonoids, a significant overall association was found. There was a suggestion of an inverse association for flavanones and isoflavones among women with body mass index <25 kg m⁻², and, for flavanones, among parous or non-users of hormone-replacement therapy women.

Conclusion:

High consumption of selected proanthocyanidins may reduce endometrial cancer risk.     

Aromatase inhibitors in the adjuvant setting: bringing the gold to a standard?

The death rate from breast cancer is falling rapidly in most developed countries due, at least in part, to the use of adjuvant endocrine therapy in women with endocrine responsive disease. In post-menopausal women tamoxifen has been the gold standard for nearly 20 years. More recently the aromatase inhibitors (AI) have become established in the management of advanced breast cancer and are being evaluated in the adjuvant setting in trials that include tens of thousands of women. Recently, data have emerged that provide increasingly strong evidence supporting the use of AI in the adjuvant setting. Anastrozole as initial adjuvant endocrine treatment has shown superiority over tamoxifen in terms of disease free survival, and impressive reductions in the risk of recurrence have been demonstrated in trials evaluating the switch from tamoxifen to an AI, either letrozole after 5 or exemestane after 2-3 years of tamoxifen respectively. The data from these recent publications, and the potential impact on routine care of women with post-menopausal breast cancer is discussed.     

How to switch from morphine or oxycodone to methadone in cancer patients? a randomised clinical phase II trial

Aim

Opioid switching is a treatment strategy in cancer patients with unacceptable pain and/or adverse effects (AEs). We investigated whether patients switched to methadone by the stop and go (SAG) strategy have lower pain intensity (PI) than the patients switched over three days (3DS), and whether the SAG strategy is as safe as the 3DS strategy.

Methods

In this prospective, open, parallel-group, multicentre study, 42 cancer patients on morphine or oxycodone were randomised to the SAG or 3DS switching-strategy to methadone. The methadone dose was calculated using a dose-dependent ratio. PI, AEs and serious adverse events (SAEs) were recorded daily for 14 days. Primary outcome was average PI day 3. Secondary outcomes were PI now and AEs day 3 and 14 and number of SAEs.

Results

Twenty one patients were randomised to each group, 16 (SAG) and 19 (3DS) patients received methadone. The mean preswitch morphine doses were 900 mg/day in SAG and 1330 mg/day in 3DS. No differences between groups were found in mean average PI day 3 (mean difference 0.5 (CI −1.2–2.2); SAG 4.1 (CI 2.3–5.9) and 3DS 3.6 (CI 2.9–4.3) or in PI now. The SAG group had more dropouts and three SAEs (two deaths and one severe sedation). No SAEs were observed in the 3DS group.

Conclusion

The SAG patients reported a trend of more pain, had significantly more dropouts and three SAEs, which indicate that the SAG strategy should not replace the 3DS when switching from high doses of morphine or oxycodone to methadone.     

Dietary total antioxidant capacity in relation to endometrial cancer risk: a case–control study in Italy

Purpose

To investigate the role of the overall antioxidant activity of diet, we estimated the relation between three dietary indices of total antioxidant capacity (TAC) and endometrial cancer risk

Methods

We analyzed data from an Italian case–control study including 454 women with incident, histologically confirmed endometrial cancer, and 908 frequency-matched controls admitted to the same hospitals as cases for acute non-neoplastic conditions. A reproducible and valid food frequency questionnaire was used to assess subjects’ habitual diet. TAC was measured using Italian food composition tables in terms of Ferric-reducing antioxidant power (FRAP), Trolox equivalent antioxidant capacity (TEAC), and total radical-trapping antioxidant parameter (TRAP). We computed odds ratios (OR) and corresponding 95 % confidence intervals (CIs) using conditional multiple logistic regression models, including terms for recognized endometrial cancer risk factors and total energy intake.

Results

TAC was inversely related to endometrial cancer risk with ORs for the highest versus the lowest quartile of 0.69 (95 % CI 0.47–1.00) for FRAP, 0.68 (95 % CI 0.46–0.99) for TEAC, and 0.68 (95 % CI 0.47–0.98) for TRAP. The relations appeared consistent in strata of selected risk factors and decreased when considering TAC without the contribution of coffee.

Conclusions

Our findings suggest a favorable role of a diet high in TAC on endometrial cancer risk, which can be partially driven by coffee consumption.