Avoidance of axillary dissection

 

• If SLNB is neg, ALND offers no OS benefit (ACOSOG Z 10, MILAN, B32)
• In clinically node neg T1 T2 no neoadjuvant chemo and no CI to WBRT, if 1-2 SLNB positive, no need to do full ALND ( ACOSOG Z11- excluded mastectomy).
• In patients undergoing mastectomy, if microscopic SLN+, no need for full ALND
• In T1/T2 cN0, if SLN+, Axillary RT better than ALND in terms of morbidity, no difference in OS or regional failure ( AMAROS, also had 17% mastectomy)
• OTOASAR trial similar to AMAROS but included pt with T < 3 cm, cN0, 1-2 SLN+, similar outcomes ie axillary RT non inferior to ALND

PNH

 When to suspect PNH?

- unexplained cytopenias

-unusual site thrombosis

-Coomb's neg hemolytic anemia

- smooth muscle dystonia--> abd pain, renal dysfunction, erectile dysfunction, pulm HTN

Investigations: Flow cytometry for CD55 and CD59. bmbx to rule out AA, MDS and bone marrow failure. If only hemolytic anemia, bmbx may not be needed. However if low WBC or plt, do a bmbx.

Classical PNH- only hemolysis, no bone marrow failure

PNH with bone marrow failure

Subclinical PNH- mild hemolysis,PNH clone < 20%

Treatment

1. C5 inhibitors: For symptomatic PNH- Ravulizumab q 8 weeks. Rav is also approved for children over 1 month.

Other C5i eculizumab ( IV q 2 weeks on maintenance) and crovalimab ( s/c) weekly for first month, then q 4 weeks.

Available through REMS program.

2.  Alternative pathway inhibitors: Iptacopan ( oral) pegcetacopan ( sub cut).  Can be used for those who have persistent or breakthrough hemolysis on eculizumab not responding to increased frequency of administration.

Can be used upfront. Avoid in those with hx of thrombosis, or excess ETOH use.

Complement-amplifying conditions, such as infection, surgery, vaccinations, or excessive alcohol consumption can worsen hemolysis when on alternative pathway inhibitors.

Danicopan--> alternative pathway inhibitor of factor D. Oral agent. Prescribe if someone on C5i has significant extravascular hemolysis.

Picture ASH Feb 2025

Metastatic bladder cancer- initial assessment

 

 Metastatic bladder cancer

Prognostic factors associated with worse survival includes :Patient factors: KPS < 80, ECOG 2 or higher, Mets to viscera, Anemia, shorter remission from prior therapy

Patient comorbidities: mycarg.org chemotoxicity calculator

Molecular alteration- FGFR3 alteration, HER 2 amplified, CPS score

Cisplatin eligibility

• World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status less than 2 (table 3) or a Karnofsky Performance Status greater than 70 percent 
• Creatinine clearance greater than or equal to 60 mL/minute 
• No significant hearing loss (measured at audiometry of 25 dB at two contiguous frequencies)
• Grade <2 peripheral neuropathy (ie, sensory alteration or paresthesia, including tingling, but not interfering with activities of daily living)
• No clinical evidence of New York Heart Association class III or greater heart failure 

Carboplatin eligibility — Good performance status but ineligible for cisplatin-based combination chemotherapy due to kidney dysfunction, neuropathy, severe hearing loss, neuropathy, and/or heart failure 

Immunotherapy eligibility —  autoimmune conditions, infectious disorders, and previous exposure to immunomodulating agents 

Enfortumab vedotin eligibility — Patients who are candidates to receive enfortumab vedotin plus pembrolizumab should receive a complete skin examination, ophthalmological assessment, measurement of glucose levels and kidney function, and a neurological evaluation. Patients with uncontrolled diabetes mellitus (HbA1c ≥8 percent or HbA1c 7 percent to <8 percent with associated symptoms of diabetes), a severe dermatologic condition, grade ≥2 neuropathy, and/or creatinine clearance ≤30 mL/minute are ineligible for this regimen.