Docetaxel for Prostate Cancer: ‘Win-Win-Win’


Adding the chemotherapy docetaxel to standard hormone therapy for both metastatic and nonmetastatic prostate cancer is a win-win-win because it improves patients’ overall quality of life (QoL), reduces the need for subsequent therapy, and is cost-effective, according to a new modeling study from the investigators of a major clinical trial.

That trial, known as STAMPEDE (Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy), helped establish that docetaxel was an effective option in the treatment of metastatic prostate cancer (Lancet. 2016;387:1163-1177). The study showed a 10-month overall survival benefit when the drug was added to androgen deprivation therapy (ADT) for hormone-sensitive metastatic prostate cancer compared with ADT alone.

However, use of docetaxel in nonmetastatic disease has been considered controversial  because the difference in survival was not as pronounced in this earlier stage of disease as it was in metastatic disease and did not reach statistical significance, as reported at the time by Medscape Medical News.

Now, the lead author of STAMPEDE, Nicholas D. James, MD, PhD, professor of clinical oncology, University of Birmingham, United Kingdom, is championing the idea.

“Results suggest use of docetaxel in selected nonmetastatic patients should be considered,” he said in a presscast ahead of the Genitourinary Cancers Symposium (GUCS) 2018, which will be held later this week in San Francisco.

The triple benefit (QoL, less need for more therapy, cost-effectiveness) seen in nonmetastatic disease is “somewhat surprising and may cause clinicians to rethink how and when they use docetaxel to treat prostate cancer,” he said.

Dr James will be presenting results from the new modeling study, which  calculated lifetime predictions of costs, changes in predicted survival duration, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. The researchers used data on both men with metastatic (M1) and nonmetastatic (M0) disease, as the trial included both populations.

Health outcomes and costs in the UK National Health Service were modeled by using EuroQol (EQ-5D), which is a standardized self-reporting tool, and resource-use data collected within the STAMPEDE trial. In the trial, standard of care was ADT for at least 2 years and, in some patients, radiotherapy. Docetaxel (75 mg/m2) was administered alongside standard of care for six 3-weekly cycles with prednisolone 10 mg daily.

The team reported that docetaxel was estimated to extend predicted survival by an average of 0.89 years for M1 patients and 0.78 years for M0 patients, compared with patients receiving standard of care.

Docetaxel was also estimated to extend QALYs by 0.51 years in M1 patients and 0.39 years in M0 patients — and the findings for this measure had a “high degree of certainty,” Dr James commented. QALY gains in M0 patients were driven by the “beneficial effect of delayed and reduced relapse,” the authors said.

Compared with standard of care, docetaxel was cost-effective in both M1 patients and M0 patients. A sensitivity analysis indicated a “very high probability” (>99%) that docetaxel is cost-effective in both M0 and M1 patients, the authors also stated. Docetaxel remained cost-effective in M0 patients because of reductions and delays in relapse; this held true even when no survival advantage was assumed.

How Does This Compare to Abiraterone?

The new data prompted Sumanta K. Pal, MD, an American Society of Clinical Oncology (ASCO) expert and urologic oncologist at City of Hope, Duarte, California, and moderator of the GUCS presscast, to think about another drug used in this setting, abiraterone (Zytiga, Janssen).

“I will be interesting to assess these results [ie cost and QoL for docetaxel] against recent data for abiraterone, an oral hormonal therapy for prostate cancer, which has similar benefit in the same settings in prostate cancer,” he told reporters.

“Abiraterone may have the benefit of improved tolerability over a short course vs chemotherapy but does require a much more extensive duration of use and further mandates concomitant intake of prednisone, a steroid,” Dr Pal said.

Understanding the cost and quality of life associated with abiraterone may help in selecting either it or docetaxel for these patients with prostate cancer, he summarized.

Press materials from ASCO further pointed out that docetaxel is much less expensive: For the average patient with prostate cancer in the United Kingdom, a course of docetaxel costs £5000 (approximately $6000) per year, compared with £24,000 ($28,800) for abiraterone.

Cutting salt could reduce need to urinate at night, study finds.


Cutting salt intake could reduce people’s need to get up in the night to urinate, says a preliminary study presented at the European Association of Urology congress in London.1

The Japanese study included 321 men and women with a mean age of 64.3 who experienced nocturia during sleep time and had a high dietary salt intake (≥8 g/day in men and ≥7 g/day in women).The participants were given written guidance and support on reducing their salt intake and were followed up for 12 weeks.

The volume and frequency of urination were measured on a frequency volume chart, and daily salt intake was estimated by examining the sodium and creatinine concentrations of spot urine samples using a formula that was adjusted for height, weight, and age.

The study found that 223 members of the group (69.5%) managed to reduce their salt intake from a mean of 10.7 g/day to 8.0 g/day. In this group the average night time frequency of urination improved, falling from 2.3 times to 1.4 times (P<0.001). In contrast, 98 subjects increased their average salt intake from a mean of 9.6 g/day to 11.0 g/day, and they found that the need to urinate increased from 2.3 times to 2.7 times a night (P<0.001).

The need to urinate during the day also reduced when salt in the diet was reduced, the researchers found. Quality of life as measured by a standard questionnaire also improved significantly from 3.6 points to 2.7 points (P<0.001) among the group who cut their salt intake.

The study has not been published in a journal so has not gone through a peer review process. However, it was reviewed for suitability and accuracy by the European Association of Urology communications group and by a specialist in the field.

The study author, Matsuo Tomohiro, of Nagasaki University in Japan, said, “This is the first study to measure how salt intake affects the frequency of going to the bathroom, so we need to confirm the work with larger studies. Night time urination is a real problem for many people, especially as they get older. This work holds out the possibility that a simple dietary modification might significantly improve the quality of life for many people.”

Marcus Drake, professor of physiological urology from the University of Bristol, UK, and lead of the European Association of Urology’s working group on nocturia, commented, “This is an important aspect of how patients potentially can help themselves to reduce the impact of frequent urination. Research generally focuses on reducing the amount of water a patient drinks, and the salt intake is generally not considered.

“Here we have a useful study showing how we need to consider all influences to get the best chance of improving the symptom.”

Figure1

References

Source:http://www.bmj.com

QUALITY OF LIFE.


Do read if you want some insight…
Years ago, Charlie, a highly respected orthopedist and a mentor of mine, found a lump in his stomach. It was diagnosed as pancreatic cancer by one of the best surgeons in the country, who had developed a procedure that could triple a patient’s five-year-survival odds—from 5% to 15%—albeit with a poor quality of life.
Charlie, 68 years old, was uninterested. He went home the next day, closed his practice and never set foot in a hospital again. He focused on spending time with his family. Several months later, he died at home. He got no chemotherapy, radiation or surgical treatment. Medicare didn’t spend much on him.

It’s not something that we like to talk about, but doctors die, too. What’s unusual about them is not how much treatment they get compared with most Americans, but how little. They know exactly what is going to happen, they know the choices, and they generally have access to any sort of medical care that they could want. But they tend to go serenely and gently.
Doctors don’t want to die any more than anyone else does. But they usually have talked about the limits of modern medicine with their families. They want to make sure that, when the time comes, no heroic measures are taken. During their last moments, they know, for instance, that they don’t want someone breaking their ribs by performing cardiopulmonary resuscitation (which is what happens when CPR is done right).
In a 2003 article, Joseph J. Gallo and others looked at what physicians want when it comes to end-of-life decisions. In a survey of 765 doctors, they found that 64% had created an advanced directive—specifying what steps should and should not be taken to save their lives should they become incapacitated. That compares to only about 20% for the general public. (As one might expect, older doctors are more likely than younger doctors to have made “arrangements,” as shown in a study by Paula Lester and others.)
Why such a large gap between the decisions of doctors and patients? The case of CPR is instructive. A study by Susan Diem and others of how CPR is portrayed on TV found that it was successful in 75% of the cases and that 67% of the TV patients went home. In reality, a 2010 study of more than 95,000 cases of CPR found that only 8% of patients survived for more than one month. Of these, only about 3% could lead a mostly normal life.
Unlike previous eras, when doctors simply did what they thought was best, our system is now based on what patients choose. Physicians really try to honor their patients’ wishes, but when patients ask “What would you do?,” we often avoid answering. We don’t want to impose our views on the vulnerable.
The result is that more people receive futile “lifesaving” care, and fewer people die at home than did, say, 60 years ago. Nursing professor Karen Kehl, in an article called “Moving Toward Peace: An Analysis of the Concept of a Good Death,” ranked the attributes of a graceful death, among them: being comfortable and in control, having a sense of closure, making the most of relationships and having family involved in care. Hospitals today provide few of these qualities.
Written directives can give patients far more control over how their lives end. But while most of us accept that taxes are inescapable, death is a much harder pill to swallow, which keeps the vast majority of Americans from making proper arrangements.
It doesn’t have to be that way. Several years ago, at age 60, my older cousin Torch (born at home by the light of a flashlight, or torch) had a seizure. It turned out to be the result of lung cancer that had gone to his brain. We learned that with aggressive treatment, including three to five hospital visits a week for chemotherapy, he would live perhaps four months.
Torch was no doctor, but he knew that he wanted a life of quality, not just quantity. Ultimately, he decided against any treatment and simply took pills for brain swelling. He moved in with me.
We spent the next eight months having fun together like we hadn’t had in decades. We went to Disneyland, his first time, and we hung out at home. Torch was a sports nut, and he was very happy to watch sports and eat my cooking. He had no serious pain, and he remained high-spirited.
One day, he didn’t wake up. He spent the next three days in a coma-like sleep and then died. The cost of his medical care for those eight months, for the one drug he was taking, was about $20.
As for me, my doctor has my choices on record. They were easy to make, as they are for most physicians. There will be no heroics, and I will go gentle into that good night. Like my mentor Charlie. Like my cousin Torch.

Like so many of my fellow doctors.

Stop Fixating on Economic Growth — Let’s Talk About Quality of Life


2016.10.12 De graaf orig

It’s necessary to promote a values transformation, away from the cruel, competitive performances and unrestrained expectations of consumer capitalism and toward a simpler, less hurried, more cooperative way of life, where work sharing is at least as important a strategy to reduce unemployment as federal jobs programs. 

Since the election, my Facebook page has been filled with postmortems, many being “I told you so” comments, seeking scapegoats for Hillary Clinton’s disastrous loss to Donald Trump. There is always someone or something who deserves quick, and primary, blame it seems — the media, the FBI, the Koch brothers, the DNC, Hillary, Bernie, the far left — pick your poison. And while all these played some role in the election’s outcome, along with xenophobia, Islamophobia, racism and misogyny, it seems to me that a fundamental and under-discussed crisis here is a crisis of values, an inability in the United States to define quality of life in anything but materialistic terms.

How in any society is it possible to glorify someone simply because, as Trump put it, “I’m rich, I’m very rich?” Millions of Americans clearly did. They somehow believe that because he is rich he is also smart, all his bankruptcies notwithstanding. They did not demand that he release his tax returns and did not recoil when he said that not paying taxes makes him smart, because they somehow believe that if taxes were not a burden for them, they too would be rich. For example, lower-income Americans are more likely to favor eliminating the estate tax than higher-income Americans. For so many, the goal is to get rich like Trump, and they accept unquestioningly Ronald Reagan’s wish to “see America always remain a country where anyone can get rich.”

The anti-government, tax-cutting paradigm that took root with California’s Proposition 13 in 1978 and Reagan’s 1980 claim that “government is not the solution because government is the problem,” still weighs heavily on us like a nightmare that we fail to confront.

All the “battleground” states that Trump won, plus countless other “red” states like Pence’s Indiana and nearly the entire South, have had government-bashing, tax-cutting GOP governors and legislatures throughout Obama’s term in office. They are almost all net “takers” of government money, while most blue states pay in more than they get. Yet, somehow, the citizens of these red states blame the Democrats for their fate — which is indeed poor. They trail blue states in almost every quality of life measure. For example, life expectancy in Massachusetts is 80.5, while in Mississippi it’s 75.0.

This certainly suggests that we haven’t done a very good job selling the value of the public sector. It doesn’t help to simply label the Democratic Party “neoliberal,” since that word has become almost devoid of meaning. There are major policy differences between the blue and red states and between the parties. To simply call both “neoliberal” obscures more than it illuminates.

Yet, perhaps the biggest similarity between the two parties is the continued acceptance of two myths — the idea of “American exceptionalism,” which even Obama constantly pays homage to (though the Right criticizes him for not being “patriotic” enough), and, the primacy of economic growth.

Neither Republicans nor Democrats challenge the growth mantra (even Paul Krugman is a cheerleader), though it is madness, as environmentalist David Brower once pointed out, to believe in unlimited growth on a finite planet. So, while Democrats want to share growth more widely and perhaps grow more via infrastructure support and alternative energy, they still believe that full employment and the end of poverty can be attained only through more growth.

The worship of GDP continues in the 5 percent growth rate that Trump promises. Even if obtainable, it would mean a near doubling of resource use in less than two decades, with disastrous environmental consequences. The idea that economic growth can be “decoupled” from resource extraction and environmental impact, has been disproven by several studies, though it is true that more resource-efficient technologies reduce the added impact of new products.

Therefore, as we try to reform the Democratic strategy, it’s necessary, as Herbert Marcuse once said, to promote a values transformation, away from the cruel, competitive performances and unrestrained expectations of consumer capitalism and toward a simpler, less hurried, more cooperative way of life, where work sharing is at least as important a strategy to reduce unemployment as federal jobs programs.

It’s necessary to understand that the values of affluenza, about which I have written at length, spur endless competition for scarce resources, and result in the overwork Bernie Sanders criticizes, as well as our declining health, our lack of social purpose, our lack of enough leisure time to be good, informed citizens and volunteer in our communities, and a host of other ills. To begin, we need to make the case that we need a new measure of well-being — indeed, one former Democratic presidential candidate, Martin O’Malley, has been a leader in developing a Genuine Progress Indicator, but such ideas never entered the debates. They should be part of our future vision.

A less acquisitive society with less focus on “hard work” will not be a poor one, either materially, or more importantly, in terms of quality of life. This is a point that must be made and something Bobby Kennedy knew back in 1968, when he first spoke out eloquently against the Gross National Product. Swedish Environmental Protection Agency studies show that 30 hours of work a week may well be optimal for well-being — 30-hour workers outperform 40- or 50-hour workers in almost every quality of life measure — life satisfaction, work satisfaction, time satisfaction, health, and importantly, in this time of climate change, lower greenhouse gas emissions.

So, perhaps it’s time to think a little bigger, a little bolder. To challenge American exceptionalism and the focus on growth. One way to challenge exceptionalism would be to focus on children. As reports by UNICEF and the Organization for Economic Cooperation and Development (OECD) make clear, American kids rank near the very bottom in almost all aspects of quality of life among rich countries, leading only Turkey, Mexico, Latvia, Lithuania and Romania.

This should embarrass us — even conservatives can’t claim that five-year-olds should pick themselves up by their bootstraps. We should also proclaim the value of quality of life vs. quantity of income. Inequality is a much broader issue than dollar income.

If we support growing the economy, we need to also ask, what kind of growth, not what rate of growth. What can grow and what must shrink if we are to live well on a finite planet. We must put a value on things — leisure time, volunteering, home gardening, caring for each other, undeveloped nature, etc. — that are now seen as without value.

Those who would privatize our public lands have bumper stickers like “Wilderness, Land of No Use” that illustrate the lack of value we bestow on many of the things of greatest value.

As we consider political strategies for 2018 and beyond, let’s go beyond our silos and current ideas of economic success and lay the groundwork for a whole new value system beyond affluenza and predator capitalism.

Cryoballoon Ablation is Noninferior to Radiofrequency Ablation


Cryoballoon ablation was found to be noninferior to radiofrequency ablation with respect to efficacy for the treatment of patients with drug-refractory paroxysmal atrial fibrillation, and there is no significant difference between the two procedures in regard to patient safety, according to late-breaking clinical trial research presented as part of ACC.16 in Chicago and simultaneously published in The New England Journal of Medicine.

The FIRE AND ICE trial, conducted by Karl-Heinz Kuck, MD, FACC, et al, is the largest randomized trial of its kind, and included participants from 16 centers in eight European countries. “The FIRE AND ICE trial demonstrated that the cryoballoon, a newer, easier-to-use ablation catheter, worked as well as the established technology, which ultimately means that more patients can be treated for atrial fibrillation without having [to go to a] specialized cardiac center,” said Kuck. “In addition, there was, in general, a low risk of procedural complications in both groups, demonstrating that catheter ablation has become much safer over the years.”

The authors wanted to compare the effectiveness of point-by-point mode applied radiofrequency ablation to that of cryoballoon ablation applied in a single step mode, a newer and less complex technique. The primary efficacy endpoint of the trial was time to first documented recurrence of AF/atrial tachycardia/atrial flutter, prescription of antiarrhythmic drugs or repeat ablation.

The multicenter, randomized, noninferior open-label trial analyzed data gathered from patients ranging from 18 to 75 years old, with symptomatic paroxysmal AF and prior antiarrhythmic drug failure. After exclusions for previous left atrial (LA) ablation, percutaneous coronary intervention or myocardial infarction within three months of enrollment, and other clinical issues, 693 patients undergoing pulmonary vein isolation were randomly assigned in a 1:1 ratio; 352 underwent radiofrequency ablation and 341 underwent cryoballoon ablation.

In-office visits were scheduled at three, six, and 12 months and every six months after. The primary efficacy endpoint occurred in 138 patients in the cryoballoon group and in 143 patients in the radiofrequency group. A pre-specified superiority test performed for the primary efficacy endpoint did not indicate a significant difference between the treatment groups. The most common treatment-related serious adverse events were groin site complication and atrial flutter or atrial tachycardia.

The authors did see significant procedural differences between the two groups. Radiofrequency ablation required less fluoroscopy time (17 vs. 22 minutes). Procedure time was shorter in the cryoballoon group, (124 minutes vs. 141 minutes). LA dwell time in the cryoballoon group was shorter as well (92 vs. 109 minutes). A favorable safety profile was observed in both groups.

“The procedure time was interesting because there are more cost pressures on the health care system for more efficient tools that keep procedures short and predictable,” Kuck said.

According to Kuck, the findings could help inform future medical guidelines on the use of different catheter ablation techniques for treating atrial fibrillation. One limitation of the study is that it did not investigate ablation for treating patients with more advanced stages of atrial fibrillation. A separate trial would be needed to assess the ablation techniques’effectiveness and safety for that patient population, he said.

– See more at: http://www.acc.org/latest-in-cardiology/articles/2016/03/23/18/25/mon-8am-fire-and-ice-effective-afib-ablation-acc-2016?wt.mc_id=twitter#sthash.M0E66Z4X.dpuf

Updated Version of White Cane Improves Quality of Life for Visually Impaired .


Two familiar items not usually paired: a robot and a cane. At the University of Arkansas at Little Rock, Cang Ye and his engineering lab team have prototyped a robotic walking stick for the blind. This robot-cane combines the basic physics of a walking stick and the technological efficiencies of a computer system.
Currently, people with visual impairments navigate using aluminum or plastic sticks with rubber ends; these tools are known as white canes or whitesticks. The robot cane is an updated version that facilitates communication between the environment, the cane and the user. The cane can both detect the user’s immediate terrain and store localized geographical information.

Man with robotic cane


It’s equipped with two cameras and Bluetooth audio. The cameras detect objects in the user’s path, such as chairs and stairs, while the audio system communicates to the user. Meanwhile, a computer holds information about recent pathways and objects within them. This allows the cane to recognize the user’s location and guide the user, much as a seeing-eye-dog would do. Like a traditional white cane, the robot cane is adjustable to different lengths.

A registered 3-D map of the experimental results from the robotic cane with a green curve showing the user’s trajectory. The robotic user walked from 1 to 2. To obtain a better view on the stairways, the user lifted and tilted the cane to scan the stairway.

This hybrid technology was designed under the National Robotics Initiative, funded by National Science Foundation and National Institutes of Health. The Ye lab partners with World Service for the Blind and Arkansas School for the Blind & Visually Impaired. Orientation and mobility specialists and students from both of these organizations help test the cane and provide feedback for device refinement. The robot cane is designed to significantly improve independent mobility and quality of life for visually impaired persons. The images accompanying this article depict an actual cane and a schematic of the prototype.

Quality of life during chemotherapy in lung cancer patients: results across different treatment lines.


Most lung cancer patients are diagnosed at an advanced disease stage and predominantly receive palliative treatment, which increasingly consists of several chemotherapy lines. We report on patients’ quality of life (QOL) to gain knowledge on QOL during and across multiple lines of chemotherapy. This includes patients with (neo)adjuvant therapy up to 3rd or above line palliative chemotherapy.

methods:

Lung cancer patients receiving outpatient chemotherapy at the Kufstein County Hospital completed an electronic version of the EORTC QLQ-C30. Linear mixed models were used for statistical analysis.

results:

One hundred and eighty seven patients were included in the study. Surprisingly, irrespective of the chemotherapy line patients reported stable QOL scores during treatment. None of the calculated monthly change rates attained clinical significance, referring to established guidelines that classify a small clinical meaningful change as 5 to 10 points. According to treatment line, 3rd or above line palliative chemotherapy was associated with the worst QOL scores, whereas patients undergoing (neo)adjuvant or 1st line palliative chemotherapy reported fairly comparable QOL.

conclusion:

The essential finding of our study is that all QOL aspects of the EORTC QLQ-C30 questionnaire remained unchanged during each chemotherapy line in an unselected population of lung cancer patients. Between treatment lines pronounced differences were found, indicating that later palliative chemotherapy lines are associated with higher QOL impairments. These changes in QOL may not primarily be related to the treatment, but rather refer to impairments due to disease progression and may be partly due to a consequence of the prior therapies.

Source: BJC

 

Pazopanib versus Sunitinib in Metastatic Renal-Cell Carcinoma.


BACKGROUND

Pazopanib and sunitinib provided a progression-free survival benefit, as compared with placebo or interferon, in previous phase 3 studies involving patients with metastatic renal-cell carcinoma. This phase 3, randomized trial compared the efficacy and safety of pazopanib and sunitinib as first-line therapy.

METHODS

We randomly assigned 1110 patients with clear-cell, metastatic renal-cell carcinoma, in a 1:1 ratio, to receive a continuous dose of pazopanib (800 mg once daily; 557 patients) or sunitinib in 6-week cycles (50 mg once daily for 4 weeks, followed by 2 weeks without treatment; 553 patients). The primary end point was progression-free survival as assessed by independent review, and the study was powered to show the noninferiority of pazopanib versus sunitinib. Secondary end points included overall survival, safety, and quality of life.

RESULTS

Pazopanib was noninferior to sunitinib with respect to progression-free survival (hazard ratio for progression of disease or death from any cause, 1.05; 95% confidence interval [CI], 0.90 to 1.22), meeting the predefined noninferiority margin (upper bound of the 95% confidence interval, <1.25). Overall survival was similar (hazard ratio for death with pazopanib, 0.91; 95% CI, 0.76 to 1.08). Patients treated with sunitinib, as compared with those treated with pazopanib, had a higher incidence of fatigue (63% vs. 55%), the hand–foot syndrome (50% vs. 29%), and thrombocytopenia (78% vs. 41%); patients treated with pazopanib had a higher incidence of increased levels of alanine aminotransferase (60%, vs. 43% with sunitinib). The mean change from baseline in 11 of 14 health-related quality-of-life domains, particularly those related to fatigue or soreness in the mouth, throat, hands, or feet, during the first 6 months of treatment favored pazopanib (P<0.05 for all 11 comparisons).

CONCLUSIONS

Pazopanib and sunitinib have similar efficacy, but the safety and quality-of-life profiles favor pazopanib

Source: NEJM

Transoral Robotic Surgery for Oropharyngeal CancerLong-term Quality of Life and Functional Outcomes.


ABSTRACT

Importance  Because treatment for oropharyngeal squamous cell carcinoma (OPSCC), especially in patients of older age, is associated with decreased patient quality of life (QOL) after surgery, demonstration of a less QOL-impairing treatment technique would improve patient satisfaction substantially.

Objective  To determine swallowing, speech, and QOL outcomes following transoral robotic surgery (TORS) for OPSCC.

Design, Patients, and Setting  This prospective cohort study of 81 patients with previously untreated OPSCC was conducted at a tertiary care academic comprehensive cancer center.

Interventions  Primary surgical resection via TORS and neck dissection as indicated.

Main Outcomes and Measures  Patients were asked to complete the Head and Neck Cancer Inventory (HNCI) preoperatively and at 3 weeks as well as 3, 6, and 12 months postoperatively. Swallowing ability was assessed by independence from a gastrostomy tube (G-tube). Clinicopathologic and follow-up data were also collected.

Results  Mean follow-up time was 22.7 months. The HNCI response rates at 3 weeks and 3, 6, and 12 months were 79%, 60%, 63%, and 67% respectively. There were overall declines in speech, eating, aesthetic, social, and overall QOL domains in the early postoperative periods. However, at 1 year post TORS, scores for aesthetic, social, and overall QOL remained high. Radiation therapy was negatively correlated with multiple QOL domains (P < .05 for all comparisons), while age older than 55 years correlated with lower speech and aesthetic scores (P < .05 for both). Human papillomavirus status did not correlate with any QOL domain. G-tube rates at 6 and 12 months were 24% and 9%, respectively. Greater extent of TORS (>1 oropharyngeal site resected) and age older than 55 years predicted the need for a G-tube at any point after TORS (P < .05 for both).

Conclusions and Relevance  Patients with OPSCC treated with TORS maintain a high QOL at 1 year after surgery. Adjuvant treatment and older age tend to decrease QOL. Patients meeting these criteria should be counseled appropriately.

Source: JAMA

 

Effect of thrombolysis with alteplase within 6 h of acute ischaemic stroke on long-term outcomes (the third International Stroke Trial [IST-3]): 18-month follow-up of a randomised controlled trial.


Background

Few data are available from randomised trials about the effect of thrombolysis with alteplase on long-term functional outcome in patients who have had acute ischaemic stroke and no trial has reported effects on health-related quality of life. A secondary objective of the third International Stroke Trial (IST-3) was to assess the effect of thrombolysis on such outcomes at 18 months.

Methods

In this open-label, international, multicentre, randomised, controlled trial, 3035 patients with ischaemic stroke from 12 countries were randomly allocated within 6 h of onset via a secure central system to either intravenous alteplase (0·9 mg/kg; n=1515) plus standard care or standard care alone (control; n=1520). 2348 patients were scheduled for 18-month follow-up. For our main analysis, survivors were assessed at 18 months with the Oxford handicap scale (OHS; the primary outcome was the adjusted odds of OHS score 0—2). We also used the EuroQoL (EQ) instrument and asked questions about overall functioning and living circumstances. We analysed the OHS and the five EQ domains by ordinal logistic regression and calculated the mean difference between treatment groups in EQ utility index and visual analogue scale score. Analyses were adjusted for key baseline prognostic factors. This study is registered with controlled-trials.com, number ISRCTN25765518.

Findings

At 18 months, 408 (34·9%) of 1169 patients in the alteplase group versus 414 (35·1%) of 1179 in the control group had died (p=0·85). 391 (35·0%) of 1117 patients versus 352 (31·4%) of 1122 had an OHS score of 0—2 (adjusted odds ratio [OR] 1·28, 95% CI 1·03—1·57; p=0·024). Treatment was associated with a favourable shift in the distribution of OHS grades (adjusted common OR 1·30, 95% CI 1·10—1·55; p=0·002). Alteplase treatment was associated with significantly higher overall self-reported health (adjusted mean difference in EQ utility index 0·060; p=0·019). The differences between the groups in visual analogue scale score and the proportion living at home were not significant.

Interpretation

IST-3 provides evidence that thrombolysis with intravenous alteplase for acute ischaemic stroke does not affect survival, but does lead to statistically significant, clinically relevant improvements in functional outcome and health-related quality of life that are sustained for at least 18 months.

Source: Lancet