Clinical Oncology - Science topic

Vipulbhai VIRABHAI Solanki Thank you for your time and comments sir, but this is not the type of course I was looking sir, as I want a certified course which teaches chemo and radiation oncology whose entry requirement is a MDS oral medicine and radiology from India, for me to practise as a clinician back here in India sir.

Yes, neoadjuvant systemic therapy is now considered standard practice for following subsets of breast cancer patients:

1. Inflammatory breast cancer

2. cT4 disease

3. cN2 or cN3 disease

4. Operable breast cancer with triple negative or HER2 +ve molecular subtype with cT2/N+ or higher disease stage

5. Large primary tumor relative to breast size, or when cN+ likely to become cN0 with neoadjuvant systemic therapy to facilitate breast conservation

The median overall survival of glioblastoma is around 10-12 months in population-based studies. This is actually an improvement from 4.9 months between 1984-1994. MGMT promoter methylation is a prognostic and treatment predictive marker with better outcomes and better response to temozolomide. Pancreatic adenocarcinoma has more treatment options available including biomarker based treatments, however GBM is continuing to be a hard nut to crack.

Currently, treatment responses are assessed on the basis of measurement of tumor size before and after treatment with serial conventional radiography, such as chest X-ray, computed tomography (CT) or magnetic resonance imaging (MRI)

The survAUC R package provides a number of ways to compare models link: https://stats.stackexchange.com/questions/181634/how-to-compare-predictive-power-of-survival-models

First thing i would like to comment on it that you may change the clone of CD20, check CD19 as well if they are even few?

Secondary, The absence B cells might be the drug effect (Like: Rituximab or any alternative/traditional medicine).

Do you have the data? Why not train a model like Mask R-CNN on it and deploy in the wild.

You can use the TCGAbiolinks package in R

I think its important to keep in mind the properties of the tumor and incorporate direct targeting strategies to tumors. I think that biotechnological advances are paving the way for better clinical outcomes. Drug delivery systems need to be designed to mimic the in vivo environment and computer aided simulations are a growing resource for it.

Hi John Schloendorn , Thanks a lot for your reply. I might have phrased my question in a wrong manner. 100% transfection efficiency is impossible, let's say it is 20% efficient. Is it possible to still transfect all cancer cells in a patient with repeated administrations each with 20% efficiency, given that the treatment is selective and non-toxic? It seems like non-viral transfection is more stochastic, in a sense that it in principle can transfect any cell, it just happens that it doesn't, so with enough repeated administration it should be able in principle to transfect all cells, right? Thank you very much for your time. Your experience is invaluable on this matter. I am asking for a research proposal I have made, where this issues now stands out.

Development, activation and contraction is more tightly regulated in T cells v B cells. Particularly the latter, so you are less likely to see t cell lymphoma secondary to chronic immune stimulation for example malt lymphoma. Also, ebv. B cells express cd21 whereas t cells only transiently do so during thymus development. So ebv causes hl, bl, mzl, malt, and dlcbl in b cells but basically, only extranodal nk/t cell lypmphomas in the cells as I recall. 97% of adults are ebv seropositive.dlbcl is the most common lymphoma in the us, roughly 15% is eber+.

Please bear in mind that there is a large interindividual variability in the bioavailability and therefore the plasma concentration of parent mycophenolate and active metabolite. The variation can b as large as 30%. You may consider checking the plasma concentration in critical cases.

The breast cancer treatment is similar in both, female and male. And this treatment may change by the stage, molecular profile (the last TNM by the AJCC).

The options are medical treatment (chemotherapy, anti-hormones, anti-her2, inmunotherapy), surgical options are more limited, normally in the male the surgery is a radical mastectomy w/wo sentinel node Vs LAD, and the third option like treatment is the radiotherapy.

I am intertesting

At least a few hundred to establish a reliable research. I think you have enough samples here.

Anticancer drugs follows log-kill Hypothesis I.e kills constant fraction of cells because of the specificity of the chemotherapy drugs to the cell cycle of the cancer. Example is use of Cytarabine in treatment of leukemia.

Wow, Barry, Renan can now go wild.

Those are the most important references.

I recall the frustrations of a US doctor who penned that as:

Death by Prescription - Dr Ray D Strand

Why unexpected!? The knowledge that such results should be expected is available at least from 1990s.

To me this is a great injustice! The financial burden must have been put mainly on the hospital and the medical physicists put in jail. After each maintenance the medical physicists must perform the appropriate QA and assure that the LA is in adequate condition to treat patients. On the other hand the phrase “the people driving the LA“ is puzzling, pointing probably towards the lack of medical physicist there. If this is so – the director of the hospital and the minister of health must have been put on trial as well. That’s my verdict :).

This paper may be useful:

Experimental mammary carcinogenesis - Rat models.

Alvarado A, Faustino-Rocha AI, Colaço B, Oliveira PA.

Life Sci. 2017 Mar 15;173:116-134. doi: 10.1016/j.lfs.2017.02.004. Epub 2017 Feb 8. Review.

Best regards,

Daniela

Thank you to everybody! Is it the same for Current Hematologic Malignancy Reports Journal?No publication fees?

Thank you

Please have a look at these useful links.

There is no known medication or therapeutic technique that is able to completely prevent malignancies, oral or otherwise. Anyone who claims that metformin completely prevents Breast cancer is either a misinformed medical lay person, or a quack practitioner.

Hi dear Christian Neumann

i think the following paper can help you

best and kind regard

Yes. there is a technique names as BH3 profiling which predict the interplay between Bcl2 family members and response to drugs. Anthony Letai from HMS developed this technique.

You may look the levels of tumor markets, if with elevated alphaphetoprotein, it does have a nonseminoma component; however gold standard for the diagnosis is pathology specimen result, so a biopsy should be done.

I am afraid that by the time blood test is positive - that is cancer cells are in the circulation - it may be too late. Nevertheless, it seems to be a step in the right direction

Cancer pattern and outcomes in low-middle income greatly differs from that of high income countries. It will also vary between countries within the low-middle income groups. Mostly, cancers of the esophagus, stomach, mouth, lungs, and pharynx in men, and uterine cervix, breast, ovary, stomach, esophagus, and mouth in women are commonly seen in India. Next, is the stage at diagnosis. Most or around 80% of all cancer patients are diagnosed in advanced stages (Stage III and IV). Thus, the outcomes to conventional treatments are relatively poor in comparison. The late diagnosis results due to lack of specialized services in the rural or under develop areas, low level of cancer awareness , and virtual absence of population-based cancer screening contributes to the late diagnosis of cancer in low-middle income countries. In India for example, more than 70% of our population resides in rural areas, however, almost every cancer diagnostic and treatment centers are located either in urban or semi-urban regions. This also contributes to drop-out during the course of treatment leading to incomplete or sub-optimal treatment, and thus poor outcomes. There are many gaps that needs to be addressed in low-middle income countries to fight cancer, given its socio-economic impact in these countries. I hope this would be useful .

You can use DPPH assay and MTT assay

Hyperuricemia in this case might be due both to an increased cell lysis- of probably normal cells due to the chemotherapy the child gets along with a reduced excretory capacity of the remaining kidney. Renal function should be thoroughly assessed as well as possible involvement of the second kidney with another Wilms tumor- which might be the case for so young kids presenting with Wilms tumor before 1 year of age. 

You can try apatinib or  sorafenib or Traditional Chinese Medicine

I am sure that chemotherapy can not play a definitive role in management. Surgery is absolutely necessary.

Dear Stephan, this article, which I enclose, is not on the drug combinations in oncology. However, it addresses the issues of effectiveness, ethics and costs related to the introduction of new oncology drugs. I hope it will be useful to you.

Best regards, Maurizio

Dear Dr Reza

i recommend to read this case report:

Aggressive Angiomyxoma of Vulva Which Grew with Pregnancy and Attained a Huge Size Rarely Seen in Literature

Vandana Sinha,corresponding author Kalpana S. Dave, Ronak P. Bhansali, and Ruchi S. Arora

Author information ► Article notes ► Copyright and License information ►

Go to:

Introduction

Aggressive Angiomyxoma (AA) of the pelvis and perineum was identified as a distinct clinicopathologic entity in 1983 [1] with less than 250 cases reported since then. The tumor usually arises in women of the reproductive age group with peak incidence in the fourth decade. Few cases of its occurrence outside the pelvis have been reported.

Go to:

Case Report

A 43-year-old female came to our OPD with complains of a growth over her private parts for the past 10 years and difficulty in walking for the past few days. She had delivered by Cesarean Section 9 months ago. The tumor increased gradually for 9 years, but grew suddenly during and after her pregnancy.

On examination, there was a huge mass arising from the left labia majora of about 55 × 45 × 45 cm with a broad pedicle (Fig. 1). The skin over the tumor was smooth, intact, and without any obvious nodularity. The right labia majora had multiple warts of 2–12 mm in size, also involving the peri-anal region.

Fig. 1

Fig. 1

Angiomyxoma of vulva arising from left labia majora with multiple warts on right labia majora

Pelvic examination was normal. There were no palpable lymph nodes. Biopsies from the large mass diagnosed angiomyxoma and biopsies from the warts diagnosed them as fibroepithelial polyps.

Her routine investigations, Pap Smear were normal. CT scan showed the presence of 53 × 43 × 46 cm sized heterogeneously enhancing soft tissue density lesion involving the left labia and perineum.

A wide excision of the tumor with adequate tumor-free margins and primary closure was done. There was no significant blood loss during the surgery. Histopathologic examination of the excised mass confirmed angiomyxoma, which was further confirmed by immunohistochemistry. The tumor was an infiltrating, diffuse, very low cellular spindle cell tumor with extensive myxoid areas and thick and thin blood vessels with foci of lymphocytes around the blood vessels. The base of the resection was free of tumor. She is symptom free for the past 8 months.

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Discussion

Aggressive Angiomyxomas are benign tumors. The term “aggressive” refers to the tumor’s locally infiltrative and recurrent nature, but with rare distant metastases [2].

In our case, AA showed the typical insidious growth pattern. Patients can present with an asymptomatic perineal nodule or a pelvic mass diagnosed on imaging studies. Our case also reflects the possible hormone dependence of this tumor as its growth was pregnancy related. Estrogen receptor positivity was also seen in the immunohistochemistry.

Pre-operative diagnosis helps in planning the extent of excision and patient counseling. However, the rarity of these neoplasms and a lack of typical features make it a difficult pre-operative diagnosis. They are misdiagnosed as labial, Bartholin’s, or Gartner’s Cyst and are diagnosed histologically after surgical excision.

Magnetic Resonance Imaging accurately detects the trans-levator spread and relation of the mass with the anal sphincter, urethra, bladder, and pelvic side-wall.

Tumor recurrences are high and can be seen even within 6 months from initial resection. There is no proven therapy for recurrences. Radiotherapy, selective angiographic embolism, hormone antagonists like tamoxifen, or GnRH analogs are also treatment options, but their role is still unclear.

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Conclusion

Angiomyxomas are rare tumors. Complete surgical excision is necessary to prevent recurrence. Patient counseling, individualization of each case, and long-term follow-up are essential.

Best wishes

Dear Wael, 

check with the authors to these papers here on RG: 

Hi Omursen!

Literature search reveals that humoral responses were independent of inhaled corticosteroid use (even high-dose inhaled corticosteroid use) in one study of 294 patients with asthma  receiving influenza vaccine156 and another of 162 patients with chronic obstructive pulmonary disease taking inhaled steroids (87 patients), oral steroids (33), and no steroids (42). Corticosteroids alter immune function through direct effects on gene transcription and have broad effects on non-lymphoid and lymphoid cells.144 Corticosteroid use predisposes patients to infections, particularly with doses higher than 10 mg/day and cumulative doses higher than 700 mg.

many thanks!

I think a partial pericardiectomy and biopsy will both help symptomatically and will probably give the diagnosis.  Malignancy should be high in the differential especially sonce the last effusion was bloody. You can also do a mammography and a thorough skin examination. Please let us know of the progress. 

Hi Berrin, Prof Cerwenka´s lab from DKFZ, Germany works extensively on NK cells. Please follow their papers. Miltenyi offers a human NK cell isolation kit and I know that their lab uses that. They use a triple cytokine cocktail for expansion. Please follow their lab papers for anything related to NK cells.

Sustained effector function of IL-12/15/18-preactivated NK cells against established tumors.

Ni J1, Miller M, Stojanovic A, Garbi N, Cerwenka A.

IL-12-producing monocytes and HLA-E control HCMV-driven NKG2C+ NK cell expansion.

Rölle A, Pollmann J, Ewen EM, Le VT, Halenius A, Hengel H, Cerwenka A.

Hope it helps. All the best!

Changting's response is very helpful. Thank you so much! I will try to contact you and talk more about this.

I do not know at all wether the attached article can be of help.

Best regards

Robert

It has recently been reported that BRAF, KRAS oncogene mutant colorectal cancer cells highly depend on glycolysis as compared with other kinds of colon cancer cells.  BRAF, KRAS oncogene mutant colorectal cancer cells are known to exhibit resistance to EGFR inhibitors such as gefitinib. Therefore, vitamin C which consumes NADPH and GSH after uptake via GLUT1 shows therapeutic effect due to the imbalance of redox stress and impaired ATP synthesis. 

Dear Ms. Alia .. this is very interesting thought since many people encourage ladies to do BSE without looking to the available evidence ..

Breast self-examination (BSE) has been compared with usual care (no screening activity) and has not been shown to reduce breast cancer mortality.

1st RCT study done in Russia " Results of a prospective randomized investigation [Russia (St.Petersburg)/WHO] to evaluate the significance of self-examination for the early detection of breast cancer ". (see the link)

2nd RCT study done in China " Randomized trial of breast self-examination in Shanghai: final results. (see the attached full text)

both studies showed no benefit of doing BSE compared to no screening and led to more breast biopsies and diagnosis of more benign breast lesions.

3rd link from NCI .. very helpful for more info about BSE & CBE 

Best Regards

If we use FIGO staging, it clearly states that any distant metastasis means stage IVB. SO, ovarian metastasis is IVB. 

If we use TNM, then of course M1

Dear Dinesh, 

If NCE means New Chemical Entities check this out: 

You don't happen to have the publication available somewhere ... and a photo of Thomas Ashworth?

I am dealing with invertebrate tissues but my supervisor ifor bowen has a lot of papers about cancers you can search for i.d. bowen and also cathrin saraf

Dear Silvie,

maybe our study design (regarding a training program in lung cancer patients) is helpful in your context: http://linkinghub.elsevier.com/retrieve/pii/S155171441300195X

thanks for reply.

please take  a look at the following example:

we have  fixed concentrations of a variable( categorical). let's say, 0, 10 and 20 ug. and we have four different concentration of each variable, let's say, 0, 10,20 and 40 ug. in the latter, each group has a concentration(continuous). please take a look at the attachment file.

so now, I am wondering to know whether there is any significant combination between each different concentration (I mean drug interaction or combination).

please note that these measuring were repeated in three different days.

I want to know if each concentration  is significant per se or when they are combined.

Thanks,

We have C3H3BrO3 (3-bromo-2-oxo-propanoicaci;3-bromopyruvate) Molecular Weight 166.96

If U need - ask on ccmt@mail.ua

Brainlab has worked well.

Yes. Seen a few patients. Usually need a combined surgical and adjuvant radiotherapy approach of treatment. 

Thanks! Dear Yoshida for your observation, but, have you any analysis of alpha fetoprotein in the evolution of any of those patients that developed tumor even above 70yrs? 

Had my first experience of educating nurses on cancer palliative care. As cancer palliative care is a new concept for Sri Lankan nurses the module and the DVD on cancer palliative care we prepared  were appreciated by the nurses.

The most  active agents include vincristine, actinomycin D, high dose cyclophosphamide, doxorubicine, ifosfamide , topotecan and etoposide. The combinations of these drugs are effective in progressive and recurrent PNET

Thank you for your answer. I will be trying this during the week.

Con'td: once you have set up the administration mode (and once again I strongly encourage you to choose the subcuntaneous continuous perfusion - beware, take the smalest osmotic pumps available (even if Alzet claims that bigger ones can fit into 25 g mice, it's just weird)), and next  just make a basic translation from human-to-mice dosing by considering that a normal 70 kg adult is about 1.73 m² (obviously this is quite variable, but this will give you the range) - depending on the mg/m² dosing  of the 5-FU regimen you are referring to in patients (quite variable as well, depending the protocol), then you can translate into mice eventually.  I have not made the calculations, but 132 mg/kg a day for 5 days by direct injection looks quite high indeed - having said that, switching to continuous infusion may improve the tolerance. Good luck!

According to Saka HK et al of Harvard Medical School, intrahepatic cholangiocarcinoma and subsets of neural, hematopoietic and bone tumors are characterized by frequent gain-of-function mutations in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes which acts through a novel mechanism of oncogenesis, producing high levels of the metabolite 2-HG, which interferes with the function of α-ketoglutarate-dependent enzymes that regulate diverse cellular processes including histone demethylation and DNA modification. Thus, a form of differentiation therapy is possible in clinical application to inhibit the mutant enzymes. And I think probably you are right in saying that clinically we can use the metabolite 2-HG to classify whether the tumors are IDH-mutant or wild-type which may have different tumor behaviors and tumor biology.

Many highly effective agents , including anthracyclines and trastuzumab, are associated with well-described risks of short- and long-term cardiac events. As these agents are often used with curative intent, maximizing the benefits while reducing cardiac risks has become a priority in oncologic management, as well as monitoring for late-term toxicity.

Additionally, given the influx of novel biologic therapies designed to fulfill unmet medical needs, efforts are needed to promote strategies for risk detection and management to avoid dangerous toxicities which may impede development of and patient access to new agents.

Dear Dr. Irfan,

Thank you so much for the information. We had some experience with the Diode laser in cordectomy for bilateral VC palsy too, and the results are encouraging; though we are yet to write about it. For the patient selection in the early laryngeal cancer, i quite agree with you because the outcome matters alot to both the patient, the surgeon and the system at large. My regards.

Dr. Kirfi, AM

Nigeria

In fact it may be better to clarify your question: do you want to subclassify by any means (this is usually easily done by light microscope by pathologist) as  Dhiraj mentioned; or by molecular subsets?

Thanks Konstantine, this is a very thorough and comprehensive review on extended hormonal therapy involving AIs, covering a lot of aspects on a subject that has not clearly answered yet. In my practice, the most common problem - and difficult to answer without solid data - is what to do with those patients who started initially with an AI and now reach 5 or (more difficult) 10 years (I use to extend AIs for more than 5 years if there are no complications). CM.

yes

Radioactive therapy with iodine 131 (131 I) is indicated to ablate residual normal thyroid and to treat functioning metastases in differentiated thyroid tumors. Because pediatric patients are few and the prognosis is generally excellent, 131I is usually recommended only for patients with extensive unresectable cervical nodal involvement, invasion of vital structures, or distant metastases.

Ample evidence suggests that more extensive surgery is associated with lower rates of recurrence. Surgery is associated with clear and definable rates of complications that can be minimized when surgery is performed by high-volume thyroid surgeons. Evidence shows that, when properly applied, RAI is associated with lower recurrence rates. Evidence also shows that DTC is associated with an increase SPM risk, which reflects intrinsic factors related to having DTC itself. Evidence also suggests that relatively high doses of 131I may contribute to an increased risk of SPM. Thus, the proven benefit of 131I in preventing cancer recurrence and cancer-related deaths needs to be weighed against potential long-term risks.

Based on the constellation of the above information, the following recommendations are made for children with DTC (Figs. 5 and and66).

The decision for treatment does not depend on the chronologic patient age but on the biological age. At this monet I have a lady aged 71 years who is getting ready for allogeneic tranplant after 2nd. remission of AML. 

Radiation is another thing, there is no contraindication, but these are the ages with higher incidence of COPD and other pulmonary problems that are important risk factors for invasive fungal diseases...

You can use G-CSF for the neutropenia; it might exacerbate the patient's joint problems; however, he could benefit from it, and you can combine it with extracorporeal photopheresis (ECP).

There is a good publication on Augmented Hyper-CVAD that combines Hyper-CVAD with Peg-Aps (and much more steroids than classical Hyper-CVAD). This is associated with toxicities (mainly sepsis/necrotising fascitis!). We at SQUH Oman usu the classical Hyper-CVAD augmented with Peg-Aps (2500 units/m2 I.V.) on Day 1 of A  part and Day 5 of B part and i think it is of major benefit based on previous studies assessing the addition of peg asp to a number of protocols. 

our studies in Nude mice showed the ineffectiveness of this Protocol.

Action pyrimidine drugs had no effect on the cells (benign kladochnye line adenoma intestine, prostate and others) both in vitro and in vivo.

Protocols on request.

PET-CT is great if readily available. Screening for pulmonal filiae is also paramount, since it is the most likely location for metastasis.

Sir,

True nodular melanomas NEVER arise in a nevus. They always arise de novo, which means they are nodular from the very beginning. This is the definition of nodular melanoma. However, vertical growth phase in already present superfitial spreading melanoma (SSM) is usually mistaken for nodular melanoma. Vertical growth phase looks like a nodule, but it is NOT a nodular melanoma since it has its horizontal phase of SSM.

 Chances to miss melanoma and to allow to develop into vertical growth phase are zero if regularly followed-up with dermatoscopy.

Of course,

We recently started using targeted panels and exome sequencing in the clinical practice mostly for targeted therapies in lung and colon cancer as well as melanoma. It is a rapidly changing field that is destined to grow especially as price continue to drop.  The real benefit will be as we are able to gather more exome or whole genome data on cancer genomes.  We will be better able to determine tumour heterogeneity and evaluate reasons for treatment failure.  Eventually this will be a front end analysis that will be more important than histopathology and radiology.

You have to treat your patient as acute lymphoblastic leukemia with extranodal involvement.

a recent study presented at ASCO showed there was no benefit in early ADT for PSA relapse,until the occurence of clinical metastatic disease

Dear Anna

I think there is no clear guidelines for the treatment of concurrent RCC and CML.  The determination of the CML status as primary or secondary is important.

I think after nephrectomy the determination of suspected getetic mutation is important before begining Sunitinib, sorafenib or Beva.

The combination of two target therapies is effective , but what is mandatory to register the genetic mutation during treatment.

Here are the 2013 guidelines from the American Society for Apheresis. It is well researched and provides recommendations based on published literature with stratification of published literature by strength. http://italkid.org/Guidelines%20on%20the%20Use%20of%20Therapeutic%20Apheresis%20in.pdf

Some of you may be interested in the free online resources available through the 'Palliative Care Curriculum for Undergraduates (PCC4U)' project.  PCC4U promotes the inclusion of palliative care education as an integral part of all medical, nursing, and allied health undergraduate and entry to practice training, and ongoing professional development.  Free learning modules (with video vignettes) are available on the following topics: Principles, Communication, Assessment, Optimisation, Multidisciplinary Care, Aboriginal Populations, Caring for Children and Culture-Centred Care.  Also available is a simulation scenario - instructional materials to support the implementation of a palliative care high fidelity simulated learning activity for health care students using an advanced patient simulator (you need a mannequin, associated software and clinical laboratory set up etc).  Visit:  www.pcc4u.org .

@Pawel: Thanks for reply! Yes, I am aware of the titanic TTN and MutSigCV paper. Some papers even excludes TTN mutations right before any analysis. But, there are many muscular disorders resulted from TTN mutations. It is not entirely impossible that TTN mutations are not significant. Also, the review paper showed that the mutated rate of TTN in HCC is about 4 -10%. It conflicts with the idea that somatic mutations of TTN is frequently seen. I mean, the assumption of MutSigCV's paper is indeed charming. I love it. But, it doesn't mean that mutated TTN has no chance to contribute  in tumorigenesis. It is indeed very difficult to validate mutations on TTN because of its size. It is indeed that TTN is low abundant and may not have detectable expression levels (RNA and protein). Then, where did the citation of the review paper comes from? By the way, IntOGen considers somatic mutations in TTN as "driver mutation" in lung and bronchus cancer data from TCGA.

Thank you very much for your replies. If "prevailing scientific evidence does not support claims" but practitioners of alternative medicine believe ozone has therapeutic benefits, should more extensive research be funded?

if so, I think you may do a microarray experiment first. Then you will find which pathway could change significantly. The drug may influence the modification of those pathway members, such as phosphorylation and acetylation.

One very interesting point in history of oncology:

Wilhelm Waldeyer (A german anatomist who invented terms like "chromosome", "Neuron" etc. was the first who stated that cancer develops from one single tumor cell. I think in 1860 and that was the opposite opinion of the great Rudolph Virchow.