state of field

[RickyScott]

Looking at editors choice, while in a really bad mood, but think legitimate points here.

New Editor's Choice citations and comments have been filed in your ACR Journal Advisor Radiation Oncology library.

This month's titles include:

• Breast: Refined estimates of local recurrence risks by DCIS score adjusting for clinicopathological features: a combined analysis of ECOG-ACRIN E5194 and Ontario DCIS cohort studies. Great, can we eliminate xrt? Unless comedo, high grade dcis or young pt, we know xrt is optional in this setting.
• 
  
• 
  
• Breast: A biological signature for breast ductal carcinoma in situ to predict radiotherapy benefit and assess recurrence risk
• can we eliminate xrt?
• 
  
• Central Nervous System: Updates in the management of intradural spinal cord tumors: a radiation oncology focus.

who cares, whatever the tumor is, arent you just going to take it to 45-50 Gy/spinal cord tolerance.

• Gastrointestinal: Tumour regression after radiotherapy for rectal cancer - Results from the randomised Stockholm III trial.

can we shorten radiation schedule in another site?

• Head and Neck / Skin: Effect of Doxepin Mouthwash or Diphenhydramine-Lidocaine-Antacid Mouthwash vs Placebo on Radiotherapy-Related Oral Mucositis Pain: The Alliance A221304 Randomized Clinical Trial.

Many of us with a lot of experience in head and neck always knew "magic" mouthwash was not magical, and should just be giving the lidocaine

• Health Services Research: Variations in Medicaid Payment Rates for Radiation Oncology
• medicaid suck unless you are in a handful of states
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• Lung and Mediastinum: Local Consolidative Therapy Vs. Maintenance Therapy or Observation for Patients With Oligometastatic Non-Small-Cell Lung Cancer: Long-Term Results of a Multi-Institutional, Phase II, Randomized Study.

good study, it has been discussed at length by everybody. Unfortunately, as pointed out in postings, majortiy of randomized phase II trials do not translate into phase III setting. That being said, much of our future hinges on this kind of treatment.

• Pediatrics: Curative-intent radiotherapy for pediatric osteosarcoma: The St. Jude experience.
• Dont give a XXXX. All you need to know is to send it to St Jude if you see one. (they fund flying out the patient and their family,) 99% of radoncs should not attempt to treat most pediatric malignancies.
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• Soft Tissue Sarcoma: Radiotherapy for Retroperitoneal Liposarcoma: A Report From the Transatlantic Retroperitoneal Sarcoma Working Group

so what did we learn here?

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[scarbrtj]

so what did we learn here?

May God have mercy on our souls.
In all seriousness. Let's be good at what we do. We irradiate. This is our last, first, best, greatest gift to the world. We are a marginalized specialty, always have been, always will be. We shouldn't contribute to our own marginalization. Sanctimonious, internecine silliness from ASTRO should stop. It should stop emanating from any rad onc for that matter, and any rad onc who sees it or experiences it should call out the emanator for a bit of scorn. Gentlemen, we either hang together or hang separately.

As an aside, and along the lines of the breast stuff you mentioned, a rad onc can get a sense of his/her own importance, or maybe lack thereof, by trying to give an honest answer to this question (slide courtesy Gabriel Hortobagyi from ASCO 2019 a couple days ago): how much of the huge drop in breast cancer mortality over the last ~50 years was driven by the field of radiation oncology? How would you answer as a rad onc? How might you reckon a surgeon, or a med onc might answer (top right slide is telling)? I think the ditching of mastectomy, and adoption of lump/XRT, has been a small driver; but past that point....

 

[Chartreuse Wombat]

Will Rogers smiles.

 

[deleted941485]

I don’t think any it was ever claimed that lump/RT saved any more lives than the TM or MRM. Now PMRT for certain pts

 

[scarbrtj]

I don’t think any it was ever claimed that lump/RT saved any more lives than the TM or MRM. Now PMRT for certain pts

There is actually an orgy of data that lump/XRT (BCT) gives better survival than mastectomy (MRM).
I realize this may go against a bit of conventional wisdom; wisdom which is wrong.
In a perfect world, this would be common knowledge. ASTRO would have been "pushing the counter-narrative." And so forth.
Were BCT and MRM drugs, and given the data below, BCT would already be the universal, non-controversial standard of care in low-risk breast cancers, and would have made its company billions.
Yet, MRM for early breast CA is being given instead of BCT more than ever, and its use is only increasing.
The State of the Field is weak. Literally. But we are board certified in the weak force, after all heh heh.

1. Effect of Breast Conservation Therapy vs Mastectomy on Disease-Specific Survival for Early-Stage Breast Cancer
2. ECCO 2017: Some Patients With Early-Stage Breast Cancer May Benefit More From Breast-Conserving Therapy Than Mastectomy
3. Breast conserving therapy and mastectomy revisited: Breast cancer-specific survival and the influence of prognostic factors in 129,692 patients
4. Andrew Seidman, MD, and Sabine Seisling, PhD, on Early-Stage Breast Cancer Outcomes: Breast-Conserving Therapy vs Mastectomy
5. Overall survival according to type of surgery in young (≤40 years) early breast cancer patients: A systematic meta-analysis comparing breast-conserving surgery versus mastectomy.
6. Noninferior Outcome After Breast-Conserving Treatment Compared to Mastectomy in Breast Cancer Patients With Four or More Positive Lymph Nodes

 

[medgator]

https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.15_suppl.e12073

https://ascopubs.org/doi/full/10.1200/JCO.2010.33.4714

 

[Mandelin Rain]

There is actually an orgy of data that lump/XRT (BCT) gives better survival than mastectomy (MRM).
I realize this may go against a bit of conventional wisdom; wisdom which is wrong.
In a perfect world, this would be common knowledge. ASTRO would have been "pushing the counter-narrative." And so forth.
Were BCT and MRM drugs, and given the data below, BCT would already be the universal, non-controversial standard of care in low-risk breast cancers, and would have made its company billions.
Yet, MRM for early breast CA is being given instead of BCT more than ever, and its use is only increasing.
The State of the Field is weak. Literally. But we are board certified in the weak force, after all heh heh.

1. Effect of Breast Conservation Therapy vs Mastectomy on Disease-Specific Survival for Early-Stage Breast Cancer
2. ECCO 2017: Some Patients With Early-Stage Breast Cancer May Benefit More From Breast-Conserving Therapy Than Mastectomy
3. Breast conserving therapy and mastectomy revisited: Breast cancer-specific survival and the influence of prognostic factors in 129,692 patients
4. Andrew Seidman, MD, and Sabine Seisling, PhD, on Early-Stage Breast Cancer Outcomes: Breast-Conserving Therapy vs Mastectomy
5. Overall survival according to type of surgery in young (≤40 years) early breast cancer patients: A systematic meta-analysis comparing breast-conserving surgery versus mastectomy.
6. Noninferior Outcome After Breast-Conserving Treatment Compared to Mastectomy in Breast Cancer Patients With Four or More Positive Lymph Nodes

There is definitely some magic (well, not magic, but whatever) about adjuvant radiation in breast cancer. Even after mastectomy in most women, IMO. Likely as simple as catching in-transit lymphatics or something, but it really works well. The push to minimize our role in this disease site is incomprehensible.

 

[scarbrtj]

There is definitely some magic (well, not magic, but whatever) about adjuvant radiation in breast cancer. Even after mastectomy in most women, IMO. Likely as simple as catching in-transit lymphatics or something, but it really works well. The push to minimize our role in this disease site is incomprehensible.

Agree. Now if we could only truly figure out the "magic." Like Arthur Clarke said, "Any sufficiently advanced technology is indistinguishable from magic." But we don't even have to invoke thaumaturgy. Just say, "it works." Mechanism not needed.
As opposed to say Lartruvo®™ where they didn't know the mechanism and couldn't prove it worked. But hey $500 million later no harm, no foul.

 

[radiaterMike]

Radiation may improve OS in early stage breast cancer, but I would not rely on SEER studies to support that claim. The use of population based registries, even when accounting for potential prognostic factors, is still limited by its retrospective nature. However, as RadsWFA1900 may have been trying to day, BCS with radiation has allowed for breast conservation.

 

[medgator]

Radiation may improve OS in early stage breast cancer, but I would not rely on SEER studies to support that claim. The use of population based registries, even when accounting for potential prognostic factors, is still limited by its retrospective nature. However, as RadsWFA1900 may have been trying to day, BCS with radiation has allowed for breast conservation.

There is randomized data in the pm setting too but no one seems to buy it since it is Chinese

Adjuvant chemotherapy and radiotherapy in triple-negative breast carcinoma: a prospective randomized controlled multi-center trial - PubMed

Patients received standard adjuvant chemotherapy plus radiation therapy was more effective than chemotherapy alone in women with triple-negative early-stage breast cancer after mastectomy.

www.ncbi.nlm.nih.gov

 

[scarbrtj]

Radiation may improve OS in early stage breast cancer, but I would not rely on SEER studies to support that claim.

Apologias! We are board certified in the weak force AND apologias.
But, I do not fault you for faulting data where radiation shows a superiority. OS improvements are so, so rare in radiation oncology, and here's essentially the largest database on earth with the most significant p-values (in regards to OS benefits from RT) ever. And yet, 'tis poo-pooed. Alas, the data from over a quarter million women supporting the claim that BCS has better survival than MRM is... unsupportable?
"We need phIII data to make that claim."
First, you will never get another large BCS vs MRM trial. Ship has completely sailed to the Western Lands there. Second, I trust population data from hundreds of thousands of patients which does not conflict with randomized data from thousands of patients quite a lot actually. Third, if William Wood were here, he could point us in the direction of all the randomized data which supports BCS vs MRM OS advantages... which is why he never used the MRM in early stage and counselled patients who wanted it against it.

 

[Brim]

Will Rogers smiles.

I believe the decline in mortality is see across all-comers, not separated out by stage, so this is not due to the Will Rogers phenomenon.

 

[radiaterMike]

Apologias! We are board certified in the weak force AND apologias.
But, I do not fault you for faulting data where radiation shows a superiority. OS improvements are so, so rare in radiation oncology, and here's essentially the largest database on earth with the most significant p-values (in regards to OS benefits from RT) ever. And yet, 'tis poo-pooed. Alas, the data from over a quarter million women supporting the claim that BCS has better survival than MRM is... unsupportable?
"We need phIII data to make that claim."
First, you will never get another large BCS vs MRM trial. Ship has completely sailed to the Western Lands there. Second, I trust population data from hundreds of thousands of patients which does not conflict with randomized data from thousands of patients quite a lot actually. Third, if William Wood were here, he could point us in the direction of all the randomized data which supports BCS vs MRM OS advantages... which is why he never used the MRM in early stage and counselled patients who wanted it against it.

I agree that it is worthwhile to analyze 'real world data' but the limitations should be acknowledged. RCTs are limited by the fact that the inclusion criteria exclude many of the patient that you see, and that there is probably a selection bias as well (someone who consents to a study is more likely to have the resources to go to a center that has that study, may have sought out that study, likely has a higher education - at a minimum can read the consent, higher income, etc).

Some scenarios dont need a RCT. I think one can safely say that any OS benefit or detriment for BCS vs MRM is probably small and that the benefit of BCS is not undergoing a MRM.

 

[seper]

Having published a few, I can attest that large-database based studies are not to be trusted. However, meta-analyses such as one done by Early Breast Cancer Trialists Collaborative Group are. They consistently show increase in survival after RT, don't they still?

 

[thecarbonionangle]

Funny funny! something is rotten in the state. Stench being sniffed out by potential medical students?

 

[domestique]

Apologias! We are board certified in the weak force AND apologias.
But, I do not fault you for faulting data where radiation shows a superiority. OS improvements are so, so rare in radiation oncology, and here's essentially the largest database on earth with the most significant p-values (in regards to OS benefits from RT) ever. And yet, 'tis poo-pooed. Alas, the data from over a quarter million women supporting the claim that BCS has better survival than MRM is... unsupportable?
"We need phIII data to make that claim."
First, you will never get another large BCS vs MRM trial. Ship has completely sailed to the Western Lands there. Second, I trust population data from hundreds of thousands of patients which does not conflict with randomized data from thousands of patients quite a lot actually. Third, if William Wood were here, he could point us in the direction of all the randomized data which supports BCS vs MRM OS advantages... which is why he never used the MRM in early stage and counselled patients who wanted it against it.

spot on

 

[scarbrtj]

I agree that it is worthwhile to analyze 'real world data' but the limitations should be acknowledged.

However, meta-analyses such as one done by Early Breast Cancer Trialists Collaborative Group are. They consistently show increase in survival after RT, don't they still?

We could debate all day. And of course we do! If you look at the true MRM vs BCT trials, they are quite old now, and the actual (combined) number is not that high. The last time EBCTCG looked at the true MRM vs BCT trials was late 90's. Trend lines pointed toward improved outcome with BCT...

but worse mortality perhaps linked to RT itself.
In the meantime, there is modern data from hundreds of thousands of patients (treated in more modern ways presumably) showing better outcomes with BCT.

...While these data would be considered hypothesis generating, to be further tested in a randomized clinical trial, such trials are challenging to conduct and may not always be feasible. In particular, given that surgical treatment of early stage breast cancer is predicated on patient choice, and where implications of mastectomy on patient psychosocial outcomes are substantial, a trial design that removes such choice from patients may be difficult in the current era. Therefore, innovative design and analysis approaches that build on clinical trials, integrate new knowledge and test applicability to the general population are needed.

Comparative effectiveness research has emerged as a means to compare different medical interventions and strategies of preventing and treating health conditions...

In our preliminary study using the NCDB, we used the propensity scores to match patients’ pretreatment characteristics between BCT and mastectomy groups. The results showed a significant favorable survival benefit from BCT compared with mastectomy. The initial study findings defied the conventional paradigm that the two local therapies offer equal survival benefit, and the subgroup analyses further suggested the choice of local treatment may impact the overall survival differently in the context of the tumor biology...

And onward the debate shall go, in perpetuity.

 

[deleted941485]

There is actually an orgy of data that lump/XRT (BCT) gives better survival than mastectomy (MRM).
I realize this may go against a bit of conventional wisdom; wisdom which is wrong.
In a perfect world, this would be common knowledge. ASTRO would have been "pushing the counter-narrative." And so forth.
Were BCT and MRM drugs, and given the data below, BCT would already be the universal, non-controversial standard of care in low-risk breast cancers, and would have made its company billions.
Yet, MRM for early breast CA is being given instead of BCT more than ever, and its use is only increasing.
The State of the Field is weak. Literally. But we are board certified in the weak force, after all heh heh.

1. Effect of Breast Conservation Therapy vs Mastectomy on Disease-Specific Survival for Early-Stage Breast Cancer
2. ECCO 2017: Some Patients With Early-Stage Breast Cancer May Benefit More From Breast-Conserving Therapy Than Mastectomy
3. Breast conserving therapy and mastectomy revisited: Breast cancer-specific survival and the influence of prognostic factors in 129,692 patients
4. Andrew Seidman, MD, and Sabine Seisling, PhD, on Early-Stage Breast Cancer Outcomes: Breast-Conserving Therapy vs Mastectomy
5. Overall survival according to type of surgery in young (≤40 years) early breast cancer patients: A systematic meta-analysis comparing breast-conserving surgery versus mastectomy.
6. Noninferior Outcome After Breast-Conserving Treatment Compared to Mastectomy in Breast Cancer Patients With Four or More Positive Lymph Nodes

Meta analysis showing the OS benefit. I mean there might be but really RT is for LC in this setting. It might be a lifesaver for some women but it just seems they are few and far between. I don’t think telling women they’re gonna die if they don’t get RT makes much sense. The selling point really is making sure the disease doesn’t return in the breast.

 

[scarbrtj]

Missed this. Germane.

Mastectomy May Be an Inferior Oncologic Approach Compared to Breast Preservation

 

[medgator]

Missed this. Germane.

Mastectomy May Be an Inferior Oncologic Approach Compared to Breast Preservation

Already seems to be the case in triple negative.

Increased risk of locoregional recurrence for women with T1-2N0 triple-negative breast cancer treated with modified radical mastectomy without adjuvant radiation therapy compared with breast-conserving therapy - PubMed

Women with T1-2N0 TNBC treated with MRM without RT have a significant increased risk of LRR compared with those treated with BCT. Prospective studies are warranted to investigate the benefit of adjuvant RT after MRM in TNBC.

www.ncbi.nlm.nih.gov

 

[radiaterMike]

While these papers are interesting they still don’t really show that there is a survival benefit to BCT. The Marks paper is an editorial and the study on triple negative (retrospective registry) has local control as an outcome. I still think breast conservation is the better approach for patients but I wouldn’t tell them it is to improve their survival. RadsWFA1900 has it right I think.

 

[scarbrtj]

While these papers are interesting they still don’t really show that there is a survival benefit to BCT.

"Papers are interesting."

Paper 1: MRM vs BCT, N=129,000, 1999-2005 BCT OS [0.71–0.76, p < 0.0001)], 2006-12 BCT OS [0.64–0.71, p < 0.0001)]
Paper 2: MRM vs BCT, N=132,000, 1998-2008 MRM OS [1.31, p<0.001]
Paper 3: MRM vs BCT, N=160,000, 2004-11 MRM OS [1.3-3, p<0.001]
Paper 4: MRM vs BCT, N=112,000, 1990-2004 BCT OS [0.8-0.83, p<0.0001]
Paper 5: MRM vs BCT, N=14,000, 2002-10 MRM OS [1-2.45, p<0.001]
Paper 6: MRM vs BCT, N=13,000, 1998-2008 MRM OS [1.43-1.9, p<0.0001]

Pretty interesting indeed. More than half a million patients with a combined p-value likely less than 1 in a billion showing a survival advantage to BCT.
I think what you are essentially saying is that no matter what... regardless of any data that may be presented in the future... nothing will ever convince you to change your mind that outcomes "...don’t really show that there is a survival benefit to BCT."
This I can't understand. At all. There is no equivalently impressive, internally consistent data cluster in the field of radiation oncology whatsoever, and this one is unbelievable to folks. Is it fear? Ingrained dogma? Worry about being labelled a heretic?
If you believe in anthropogenic global warming, e.g., but not a survival advantage to BCT vs MRM, there is MUCH more robust data for the latter versus the former.

 

[radiaterMike]

sigh ... what I am saying (and said earlier in the thread) is that using large population based registries to compare treatments is subject to biases.

The authors of those papers know this:
Paper 1: "Our results support the hypothesis that BCT might be preferred in most breast cancer patients ...."
"...we might have created confounding by severity."
Paper 2: "Further investigation is warranted to understand what may be contributing to this effect."
"patients in our study were selected to undergo ... based on a variety of factors, some of which may not be accounted for by our study ..."
Paper 3: "Thus, the selection biases cannot be completely diminished, although we used propensity score analysis."
Paper 4: "Many patient or tumor characteristics not reported to the cancer registry may have influenced the recommendation for and choice of lumpectomy or mastectomy."
Paper 5: "Confounding by indication may explain the observed survival discrepancy, as receipt of mastectomy may be associated with higher risk patients in practice. We were unable to account for factors ..."
Paper 6: "Observational studies, such as this, are prone to selection effects. "

I'm a radiation oncologist, so I assume we agree that BCT is better, I just don't know if OS is truly better (it certainly might be).

Anyways I have something more important to do (figure out what in the world Ricky Scott is saying in the thread "How many radiation oncologists ...")

 

[KHE88]

"Papers are interesting."

Paper 1: MRM vs BCT, N=129,000, 1999-2005 BCT OS [0.71–0.76, p < 0.0001)], 2006-12 BCT OS [0.64–0.71, p < 0.0001)]
Paper 2: MRM vs BCT, N=132,000, 1998-2008 MRM OS [1.31, p<0.001]
Paper 3: MRM vs BCT, N=160,000, 2004-11 MRM OS [1.3-3, p<0.001]
Paper 4: MRM vs BCT, N=112,000, 1990-2004 BCT OS [0.8-0.83, p<0.0001]
Paper 5: MRM vs BCT, N=14,000, 2002-10 MRM OS [1-2.45, p<0.001]
Paper 6: MRM vs BCT, N=13,000, 1998-2008 MRM OS [1.43-1.9, p<0.0001]

Pretty interesting indeed. More than half a million patients with a combined p-value likely less than 1 in a billion showing a survival advantage to BCT.
I think what you are essentially saying is that no matter what... regardless of any data that may be presented in the future... nothing will ever convince you to change your mind that outcomes "...don’t really show that there is a survival benefit to BCT."
This I can't understand. At all. There is no equivalently impressive, internally consistent data cluster in the field of radiation oncology whatsoever, and this one is unbelievable to folks. Is it fear? Ingrained dogma? Worry about being labelled a heretic?
If you believe in anthropogenic global warming, e.g., but not a survival advantage to BCT vs MRM, there is MUCH more robust data for the latter versus the former.

There's this thing that happens where people with more advanced/aggressive disease opt for more radical treatment options than people with lower risk disease and makes outcomes look worse than they really are when you compare the two.

Perplexion bias?
Reflection bias?

Something like that. I can't remember. I'm too busy memorizing the important stuff like molecular bio pathways and taqman so I don't kill somebody in clinic.

 

[evilbooyaa]

"Papers are interesting."

Paper 1: MRM vs BCT, N=129,000, 1999-2005 BCT OS [0.71–0.76, p < 0.0001)], 2006-12 BCT OS [0.64–0.71, p < 0.0001)]
Paper 2: MRM vs BCT, N=132,000, 1998-2008 MRM OS [1.31, p<0.001]
Paper 3: MRM vs BCT, N=160,000, 2004-11 MRM OS [1.3-3, p<0.001]
Paper 4: MRM vs BCT, N=112,000, 1990-2004 BCT OS [0.8-0.83, p<0.0001]
Paper 5: MRM vs BCT, N=14,000, 2002-10 MRM OS [1-2.45, p<0.001]
Paper 6: MRM vs BCT, N=13,000, 1998-2008 MRM OS [1.43-1.9, p<0.0001]

All 6 are registry/database studies. https://ascopubs.org/doi/full/10.1200/JCO.18.01074 - When database studies are compared to randomized clinical trial outcomes, their concordance rate is 40%. That means flipping a coin would give you better predictive power than a registry study.

There is likely an inherent selection bias that women with mastectomy have multifocal or multicentric disease, or other aggressive features, that is never captured in database variables. If you've never done a database analysis yourself and seen all of the potential confounders that there is no information on and thus have zero ability to control for, you won't fully understand the limitations. Registry studies are meant to be hypothesis generating, not to replace RCTs.

 

[scarbrtj]

That means flipping a coin would give you better predictive power than a registry study.

Your honor, the radiation oncologists have just made the case that the data consistently associating BCT with superior survival shows that BCT gives equal survival. And a single coin flip gives better predictive power than the repeatedly positive Bayesian inferences from multiple "looks" at half a million data points.

I rest my case your honor.