Saturday, September 30, 2023

Thrombocytopenia

 Outpatient


.fname has been referred for further evaluation and management of thrombocytopenia.

On review of records, he/she had a normal platelet count until -date. OR We have no record of last known normal platelet count.

On- date- platelet counts were (low/normal) at *. Since then there has been a gradual drop over a period of * months. The most recent platelet counts are *.

Hemoglobin and white count are normal.

Clinically, the patient denies bleeding from nose, mouth, gums or cutaneous bleeding. There is no history of rectal bleeding or melena. No history of vaginal bleeding or hematuria.

No constitutional symptoms such as weight loss, weight gain, fever, chills, abnormal lumps. Full 13 system review was as noted below. No recent vaccinations.

No history of infections such as hepatitis C or Helicobacter pylori. No history of risk factors for HIV such as unprotected sexual intercourse or needle sharing. He is agreeable to testing for these 3 infections as part of the work up.

No history of liver disease. LFT are normal. Prior abdominal imaging in *date showed no evidence of splenomegaly, or liver cirrhosis on ultrasound. The platelet count at the time of the imaging was low at *. History of alcohol intake:

No history of tobacco or recreational drug use. Marijuana* 

The patient is not pregnant. There is no family history of blood disorders or bleeding history. No family members with a history of splenectomy. No history of blood transfusion, heparin exposure, cardiac or other surgical procedures in the last 3 months.

All medications were reviewed. He was not temporally initiated on a new medication prior to the onset of thrombocytopenia.  Over the counter medications were reviewed.*

There is no history of malignancy or autoimmune condition personally or in the family.


Clinical exam:

Conjunctival bleeding

Skin petechiae/ purpura

Oral mucosa: wet purpura

Abdomen: palpable liver and or spleen

Signs of chronic liver disease


A/P:

.age yo .gender with isolated thrombocytopenia of gradual onset since *. No clinical evidence of bleeding. No associated anemia or WBC abnormalities. No hx of drug use, excess alcohol use. No hx of malignancy, autoimmune disease, new medication or liver disease. No hx of infections, recent blood transfusion, cardiac or surgical procedures.

Ddx: ITP, drug induced thrombocytopenia.

Investigations:

  • CBC, peripheral smear review, quantitative immunoglobulin, B12 level
  • Infection testing: hepatitis C, HIV, H. pylori
  • Bone marrow exam: if older 60 yr, treatment with steroids planned, rapid down trend in platelet count, anemia or WBC count issues to rule out MDS.
  • US abdomen -
  • If anemia- baseline anemia work up, B12 level, ferritin, retic count 
  • ABO, DAT

Inpatient: reference



.fname was admitted to the hospital on * for complaints of *.  Information was obtained by review of records. 

Last normal platelets:

Sudden or gradual drop in platelets since: 

Prior to this, the patient was started on * medication/ chemotherapy. hx of antibiotic or heparin ( 4T score)

No history of recent surgery, cardiac procedure, or blood transfusion. No hx of vaccination.

Current medications including antibiotics with start date:

Summary of initial work up:

  • DIC panel: fibrinogen, D dimer, FDP ( use ISTH scoring system)
  • Peripheral smear : Examine smear- 
    • clumping, giant plt--> true thrombocytopenia
    • RBC: schistocytes, spherocytes,  nucleated RBC, RBC clumping, 
    • WBC: blasts, toxic granulations, atypical lymphocytes, neutrophilia
  • B12, ferritin
  • PT, PTT
  • Blood cultures
  • Hepatitis C, HIV
  • ABO DAT

A/P Top diagnosis:  sepsis, drug-induced thrombocytopenia, immune thrombocytopenia, or surgery

Rule out life threatening conditions:  Identify if actively bleeding, new thrombosis, multiorgan failure, neurologic dysfunction, DIC,  post op or on dialysis

Ddx: Life threatening diagnosis

  • Sepsis-induced thrombocytopenia (check blood cultures and lactate)
  • Heparin-induced thrombocytopenia
  • Thrombotic thrombocytopenia purpura or hemolytic uremic syndrome (which leads to fragmented red blood cells and an increased LDH)
  • Drug-induced immune thrombocytopenia
  • Primary immune thrombocytopenia (ITP) with bleeding (very unusual in a hospitalized patient who doesn’t have a previous diagnosis of ITP)
  • Acute leukemia
  • Posttransfusion purpura (very rare)



Friday, September 29, 2023

ASCO guideline Hormone sensitive metastatic prostate cancer

 

1. Compare PEACE 1 trial with ARASENS trial?

Abiraterone added to docetaxel and ADT improved rPFS and OS. Hypertension was higher in abiraterone but neutropenia, fatigue, neuropathy, and sepsis were not increased. This was for patients with high volume disease and data are immature for low vol disease.  The median OS in Chaarted trial with docetaxel +ADT was 55 months which is 4.5 years, the same as in the SOC arm ( docetaxel with ADT). The median OS was not reached in the triplet arm.

  • Median progression-free survival was 4.46 in the triplet abiraterone arm vs 2.03 years, and median overall survival was not reached vs 4.43 years.

ARASENS: Darolutamide median OS not reached versus 45 months ( shy of 4 yr). Clear improvement in OS and all secondary factors such as rPFS, time to first skeletal event, time to next antineoplastic therapy. AE coincided with docetaxel administration.

2. Compare ARCHES versus ENZAMET trial?

Arches compared enzalutamide versus placebo in hormone sensitive met prostate ca. Although OS was not improved, multiple other factors including radiographic progression, PSA rise and initial skeletal events, pain progression were all less with enza compared to placebo with ADT. Prior docetaxel use was permitted. Low volume disease patients also benefited. Approx 24% grade 3 or higher AE.

Enzamet was similar to Arches trial but had a triplet arm with docetaxel.

3. CHAARTED trial OS: docetaxel with ADT 55 months OS, 13 months more than ADT alone in high volume disease.

4. What adverse effects should you be concerned in patients on AR inhibitors?

 These include fatigue, falls, fractures, mental impairment, rash, hypertension, and cardiovascular events. 

Darolutamide dose needs to be reduced for Child Pugh's B and Cr Cl 15-29. The dose is 300 mg BID.

During counseling for darolutamide: ask for symptoms of uncontrolled ischemic heart disease and other CV risk factors. Counsel about risk of seizures.


Apalutamide has an incidence of rash of 25%. This is more than for other AR inhibitors. Typically seen at 2.5 months.

Management: reference







Tuesday, September 26, 2023

Prostate cancer in the elderly ASCO education 2023

1. Geriatric assessment screen- G8

https://www.mdcalc.com/calc/10426/g8-geriatric-screening-tool

The G8 ranges from 0 to 17, with lower numbers associated with increasing frailty. In patients with cancer, scoring below 14 has an 85% sensitivity and 64% specificity for detecting frailty.


2. Life expectancy calculator

eprognosis by UCSF

https://eprognosis.ucsf.edu/calculators.php

3. Cognitive screening: Mini Cog Score of 3 or less indicates impairment with 89% specificity

Remember 3 objects, draw a clock face

4. My CARG chemo toxicity calculator:

https://www.mycarg.org/?page_id=2405

4. Bone health

DXA on initiation of ADT

- newly diagnosed castrate sensitive Prostate ca patients do not need antiresorptive therapy unless:

- prior fracture

-osteoporosis

-high risk osteopenia with FRAX showing greater than 20% risk of any fracture or 3% risk of hip fracture in 10 yr




Friday, September 15, 2023

Triple negative breast cancer Early stage

 1. Dose dense regimen

Use of DDAC followed by taxol- EFS and OS benefit shown in the CALGB/intergroup trial 2003 82% versus 75% DD group versus 3 week dose at 4 yr cut off.

2. Weekly taxol:

ECOG 1199 study demonstrated that once weekly paclitaxel 80 mg/m2 improved disease-free survival (DFS; HR, 0.69; P = .001) and OS (HR, 0.69; P = .019) compared with once every 3-weeks paclitaxel 175 mg/m2 administration.

3. Adjuvant after pembro based regimen Keynote 522

- if path CR--> ct pembro

-if no path CR, capecitabine if no germline BRCA, otherwise olaparib. If pre op pembro ct pembro.

CREATE-X trial as adjuvant treatment with capecitabine (1,250 mg/m2 PO twice a day days 1-14, 6-8 cycles) improved OS of patients with TNBC and residual invasive disease after NAC when compared with observation (HR, 0.52)

Olympia trial : After a median follow-up of 2.5 years, the 3-year DDFS was 87.5% in the olaparib group and 80.4% in the placebo group (7.1% difference)

Sunday, September 10, 2023

Lung cancer stage 4

1. EGFR: Osimertinib, dacomitinib 1L

2. Afatinib (1L) with or without cetuximab ( after progression on Osimertinib)

3. ALK :Alectinib, Brigatinib, Lorlatinib all 1L, Lorlatinib can be 2L

4. Dabrafenib Trametinib can do 1L in BRAF  V600E mutated

5. 2nd line EGFR exon 20- amivantamab, mobocertinib

6.  KRAS G12 C 2L Sotorasib/ adagrasib

7. MET exon 14: 1L ok tepotinib, capmatinib, crizotinib

8. ROS 1: 1L Entrectenib ( better if brain mets) crizotinib, ceritinib. Lorlatinib can be used 2L.

9.  NTRK- 1L entrectenib, larotrectinib

10. HER 2 mutated- TDxd 2L

11. RET-1 L selpercatinib/ pralsetinib



Stage 4 lung cancer and IO

Cemiplimab monotherapy PDL1 50% or higher- median OS 26 m vs 13 months 

Cemiplimab with chemotherapy median OS 22 m vs 13 m. 

Both are category 1.

Cemiplimab with chemo: The most common (≥15%) adverse reactions were alopecia, musculoskeletal pain, nausea, fatigue, peripheral neuropathy, and decreased appetite.

The recommended cemiplimab-rwlc dose is 350 mg IV every 3 weeks. 

What subgroup of patients did the cemiplimab not benefit even though the overall population benefited? PDL1< 1%, women and non smokers. Underpowered to test the benefits.







Primary CNS lymphoma

 Reference: Annals of Oncology  June 2024 ESMO guidelines Diagnosis  Recommendations • Contrast-enhanced cranial MRI is the recommended imag...