Cervical Cancer in Pregnancy (CCIP) - Comprehensive Management Overview

from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle,
    HRFlowable, PageBreak, KeepTogether
)
from reportlab.lib.pagesizes import A4
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.units import cm, mm
from reportlab.lib import colors
from reportlab.lib.enums import TA_CENTER, TA_LEFT, TA_JUSTIFY
from reportlab.platypus.flowables import Flowable

OUTPUT = "/tmp/workspace/ccip/CCIP_Management_Guide.pdf"

# ── Colours ──────────────────────────────────────────────────────────────────
DARK_BLUE   = colors.HexColor("#1A3A5C")
MED_BLUE    = colors.HexColor("#2C6FAC")
LIGHT_BLUE  = colors.HexColor("#D6E8F7")
TEAL        = colors.HexColor("#17737A")
TEAL_LIGHT  = colors.HexColor("#D0F0F2")
RED         = colors.HexColor("#C0392B")
RED_LIGHT   = colors.HexColor("#FADBD8")
ORANGE      = colors.HexColor("#D35400")
ORANGE_LIGHT= colors.HexColor("#FDEBD0")
GREEN       = colors.HexColor("#1D6A39")
GREEN_LIGHT = colors.HexColor("#D5F5E3")
PURPLE      = colors.HexColor("#6C3483")
PURPLE_LIGHT= colors.HexColor("#E8DAEF")
GREY_HEADER = colors.HexColor("#2C3E50")
GREY_LIGHT  = colors.HexColor("#ECF0F1")
GREY_MID    = colors.HexColor("#BDC3C7")
WHITE       = colors.white
YELLOW_LIGHT= colors.HexColor("#FEF9E7")

# ── Styles ────────────────────────────────────────────────────────────────────
styles = getSampleStyleSheet()

def style(name, **kw):
    base = styles[name] if name in styles else styles["Normal"]
    return ParagraphStyle(name + str(id(kw)), parent=base, **kw)

TITLE_S   = style("Normal", fontSize=22, textColor=WHITE, leading=28,
                  alignment=TA_CENTER, fontName="Helvetica-Bold")
SUB_S     = style("Normal", fontSize=12, textColor=LIGHT_BLUE, leading=18,
                  alignment=TA_CENTER, fontName="Helvetica-Oblique")
H1        = style("Normal", fontSize=14, textColor=WHITE, leading=18,
                  fontName="Helvetica-Bold", spaceAfter=2)
H2        = style("Normal", fontSize=11, textColor=DARK_BLUE, leading=15,
                  fontName="Helvetica-Bold", spaceBefore=8, spaceAfter=3)
H3        = style("Normal", fontSize=10, textColor=TEAL, leading=14,
                  fontName="Helvetica-Bold", spaceBefore=4, spaceAfter=2)
BODY      = style("Normal", fontSize=8.5, leading=12, fontName="Helvetica",
                  spaceAfter=2)
BODY_SM   = style("Normal", fontSize=7.5, leading=11, fontName="Helvetica")
BOLD_SM   = style("Normal", fontSize=7.5, leading=11, fontName="Helvetica-Bold")
CELL_H    = style("Normal", fontSize=8, leading=11, textColor=WHITE,
                  fontName="Helvetica-Bold", alignment=TA_CENTER)
CELL_B    = style("Normal", fontSize=7.5, leading=10.5, fontName="Helvetica",
                  alignment=TA_LEFT)
CELL_C    = style("Normal", fontSize=7.5, leading=10.5, fontName="Helvetica",
                  alignment=TA_CENTER)
FOOT_S    = style("Normal", fontSize=7, textColor=colors.grey, leading=10,
                  alignment=TA_CENTER)
BOX_S     = style("Normal", fontSize=8, leading=12, fontName="Helvetica",
                  textColor=DARK_BLUE)
WARN_S    = style("Normal", fontSize=8, leading=12, fontName="Helvetica-Bold",
                  textColor=RED)
NOTE_S    = style("Normal", fontSize=7.5, leading=11, fontName="Helvetica-Oblique",
                  textColor=GREY_HEADER)

# ── Helper Flowables ──────────────────────────────────────────────────────────
def sp(h=4): return Spacer(1, h)

def section_header(text, bg=DARK_BLUE):
    data = [[Paragraph(text, H1)]]
    t = Table(data, colWidths=[17.5*cm])
    t.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), bg),
        ("TOPPADDING",    (0,0), (-1,-1), 6),
        ("BOTTOMPADDING", (0,0), (-1,-1), 6),
        ("LEFTPADDING",   (0,0), (-1,-1), 10),
        ("ROUNDEDCORNERS", [4,4,4,4]),
    ]))
    return t

def info_box(text, bg=LIGHT_BLUE, border=MED_BLUE, text_style=BOX_S):
    data = [[Paragraph(text, text_style)]]
    t = Table(data, colWidths=[17.5*cm])
    t.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), bg),
        ("BOX",        (0,0), (-1,-1), 1, border),
        ("TOPPADDING",    (0,0), (-1,-1), 6),
        ("BOTTOMPADDING", (0,0), (-1,-1), 6),
        ("LEFTPADDING",   (0,0), (-1,-1), 8),
    ]))
    return t

def warn_box(text):
    return info_box(text, bg=RED_LIGHT, border=RED, text_style=WARN_S)

def note_box(text):
    return info_box(text, bg=YELLOW_LIGHT, border=ORANGE, text_style=NOTE_S)

def make_table(headers, rows, col_widths, header_bg=DARK_BLUE, alt_bg=GREY_LIGHT):
    data = [[Paragraph(h, CELL_H) for h in headers]]
    for i, row in enumerate(rows):
        bg = WHITE if i % 2 == 0 else alt_bg
        data.append([Paragraph(str(c), CELL_B) for c in row])
    t = Table(data, colWidths=col_widths, repeatRows=1)
    style_cmds = [
        ("BACKGROUND",   (0,0), (-1,0), header_bg),
        ("FONTNAME",     (0,0), (-1,0), "Helvetica-Bold"),
        ("ALIGN",        (0,0), (-1,0), "CENTER"),
        ("VALIGN",       (0,0), (-1,-1), "MIDDLE"),
        ("ROWBACKGROUNDS",(0,1),(-1,-1), [WHITE, alt_bg]),
        ("GRID",         (0,0), (-1,-1), 0.4, GREY_MID),
        ("TOPPADDING",   (0,0), (-1,-1), 4),
        ("BOTTOMPADDING",(0,0), (-1,-1), 4),
        ("LEFTPADDING",  (0,0), (-1,-1), 5),
        ("RIGHTPADDING", (0,0), (-1,-1), 5),
    ]
    t.setStyle(TableStyle(style_cmds))
    return t

# ── Flowchart helpers (drawn as table-based boxes) ────────────────────────────
def flow_box(text, bg=MED_BLUE, tc=WHITE, w=17.5*cm):
    s = ParagraphStyle("fb", fontName="Helvetica-Bold", fontSize=8.5,
                       textColor=tc, leading=12, alignment=TA_CENTER)
    t = Table([[Paragraph(text, s)]], colWidths=[w])
    t.setStyle(TableStyle([
        ("BACKGROUND",(0,0),(-1,-1),bg),
        ("BOX",(0,0),(-1,-1),1,GREY_MID),
        ("TOPPADDING",(0,0),(-1,-1),5),
        ("BOTTOMPADDING",(0,0),(-1,-1),5),
        ("ROUNDEDCORNERS",[4,4,4,4]),
    ]))
    return t

def flow_arrow(): return Paragraph("▼", style("Normal", fontSize=10,
    textColor=GREY_HEADER, alignment=TA_CENTER))

def flow_diamond(text, w=17.5*cm):
    s = ParagraphStyle("fd", fontName="Helvetica-Bold", fontSize=8.5,
                       textColor=DARK_BLUE, leading=12, alignment=TA_CENTER)
    t = Table([[Paragraph("◆  " + text + "  ◆", s)]], colWidths=[w])
    t.setStyle(TableStyle([
        ("BACKGROUND",(0,0),(-1,-1),ORANGE_LIGHT),
        ("BOX",(0,0),(-1,-1),1.5,ORANGE),
        ("TOPPADDING",(0,0),(-1,-1),6),
        ("BOTTOMPADDING",(0,0),(-1,-1),6),
    ]))
    return t

def two_col_flow(left_items, right_items, label_left="YES / N(-)", label_right="NO / N(+)"):
    """Two-branch decision flowchart using a 2-col table."""
    def col(items, bg, tc):
        rows = []
        for itm in items:
            s = ParagraphStyle("fc", fontName="Helvetica", fontSize=7.5,
                               textColor=tc, leading=11, alignment=TA_CENTER)
            rows.append([Paragraph(itm, s)])
        return rows

    left_rows  = col(left_items,  GREEN_LIGHT, GREEN)
    right_rows = col(right_items, RED_LIGHT,   RED)
    max_rows = max(len(left_rows), len(right_rows))
    while len(left_rows)  < max_rows: left_rows.append( [Paragraph("", BODY_SM)])
    while len(right_rows) < max_rows: right_rows.append([Paragraph("", BODY_SM)])

    lh = ParagraphStyle("lh", fontName="Helvetica-Bold", fontSize=8,
                        textColor=WHITE, leading=12, alignment=TA_CENTER)
    header_row = [[Paragraph("✓ " + label_left, lh), Paragraph("✗ " + label_right, lh)]]
    data = header_row + [[l[0], r[0]] for l, r in zip(left_rows, right_rows)]
    t = Table(data, colWidths=[8.5*cm, 8.5*cm])
    t.setStyle(TableStyle([
        ("BACKGROUND", (0,0),(0,0), GREEN),
        ("BACKGROUND", (1,0),(1,0), RED),
        ("BACKGROUND", (0,1),(0,-1), GREEN_LIGHT),
        ("BACKGROUND", (1,1),(1,-1), RED_LIGHT),
        ("GRID",       (0,0),(-1,-1), 0.4, GREY_MID),
        ("VALIGN",     (0,0),(-1,-1), "MIDDLE"),
        ("TOPPADDING", (0,0),(-1,-1), 4),
        ("BOTTOMPADDING",(0,0),(-1,-1),4),
        ("LEFTPADDING", (0,0),(-1,-1), 5),
    ]))
    return t

# ══════════════════════════════════════════════════════════════════════════════
#  BUILD PDF
# ══════════════════════════════════════════════════════════════════════════════
doc = SimpleDocTemplate(
    OUTPUT, pagesize=A4,
    leftMargin=1.8*cm, rightMargin=1.8*cm,
    topMargin=2*cm, bottomMargin=2*cm
)

story = []

# ─── COVER ────────────────────────────────────────────────────────────────────
cover_data = [[
    Paragraph("CERVICAL CANCER IN PREGNANCY", TITLE_S),
    Paragraph("(CCIP) — Comprehensive Management Guide", SUB_S),
    Paragraph("Stage-Wise · Trimester-Wise · Evidence-Based", SUB_S),
    Spacer(1, 6),
    Paragraph("ESGO/INCIP 2025 · ESGO/ESTRO/ESP 2023 · FIGO 2018 · NCCN 2024", FOOT_S),
    Paragraph("Berek & Novak's Gynecology · Creasy & Resnik's Maternal-Fetal Medicine", FOOT_S),
]]
cover_t = Table([[r] for r in cover_data[0]], colWidths=[17.5*cm])
cover_t.setStyle(TableStyle([
    ("BACKGROUND", (0,0),(-1,-1), DARK_BLUE),
    ("TOPPADDING",    (0,0),(-1,-1), 12),
    ("BOTTOMPADDING", (0,0),(-1,-1), 12),
    ("LEFTPADDING",   (0,0),(-1,-1), 14),
    ("ROUNDEDCORNERS",[6,6,6,6]),
]))
story.append(cover_t)
story.append(sp(10))

# ─── EPIDEMIOLOGY ─────────────────────────────────────────────────────────────
story.append(section_header("1. EPIDEMIOLOGY & KEY FACTS"))
story.append(sp(6))
epi_rows = [
    ["Incidence", "~1.2 per 10,000 pregnancies"],
    ["Rank", "Most common gynecologic malignancy in pregnancy (alongside breast cancer, melanoma, lymphoma)"],
    ["Diagnosis timing", "Usually at first-trimester cervical screening; often delayed due to bleeding attributed to obstetric causes"],
    ["Prognosis in pregnancy", "Slightly better OS (higher proportion of stage I); postpartum diagnosis carries worse prognosis"],
    ["Postpartum (within 6 mo)", "Associated with more advanced stage and significantly worse outcomes — treat immediately per non-pregnant guidelines"],
]
story.append(make_table(["Parameter", "Detail"], epi_rows,
                         [5.5*cm, 12*cm], header_bg=TEAL, alt_bg=TEAL_LIGHT))
story.append(sp(8))

# ─── STAGING ──────────────────────────────────────────────────────────────────
story.append(section_header("2. FIGO 2018 STAGING (Used Throughout)"))
story.append(sp(6))
staging_rows = [
    ["IA1", "Microscopic invasion ≤3 mm depth, ≤7 mm width"],
    ["IA2", "Microscopic invasion 3–5 mm depth, ≤7 mm width"],
    ["IB1", "Clinically visible ≤2 cm OR microscopic >IA2"],
    ["IB2", "Clinically visible, 2–4 cm"],
    ["IB3", "Clinically visible, >4 cm"],
    ["IIA", "Extension to upper 2/3 vagina; no parametrial involvement"],
    ["IIB", "Parametrial involvement"],
    ["IIIA/IIIB", "Lower vagina / pelvic wall / hydronephrosis"],
    ["IVA/IVB", "Bladder or rectum invasion / distant metastases"],
]
story.append(make_table(["Stage", "Description"], staging_rows,
                         [3*cm, 14.5*cm]))
story.append(sp(8))

# ─── DIAGNOSIS ────────────────────────────────────────────────────────────────
story.append(section_header("3. DIAGNOSIS & INVESTIGATIONS IN PREGNANCY"))
story.append(sp(6))
dx_rows = [
    ["Pap smear", "ALL trimesters", "Perform at FIRST prenatal visit"],
    ["Colposcopy", "ALL trimesters", "Safe; NO endocervical curettage"],
    ["Cervical biopsy", "ALL trimesters", "Safe; perform for grossly suspicious lesions"],
    ["Conization (diagnostic)", "AVOID in 1st trimester", "Abortion risk up to 33%; prefer 2nd trimester; only if cancer cannot be excluded by biopsy/colposcopy"],
    ["MRI (no gadolinium)", "ALL trimesters", "PREFERRED imaging — safe; use for local staging and tumor extent"],
    ["Chest X-ray + shielding", "ALL trimesters", "Acceptable; fetal dose <0.001 cGy"],
    ["CT abdomen/pelvis", "Use with caution", "Fetal dose ~1–2 cGy; use only when essential; avoid in 1st trimester"],
    ["PET scan", "AVOID", "Limited fetal safety data; use only if no alternative"],
    ["SLN biopsy (⁹⁹ᵐTc only)", "1st/2nd trimester", "Feasible; NO blue dye (Patent Blue V); ESGO/INCIP 2025 supports this"],
    ["Amniocentesis", "3rd trimester", "For fetal lung maturity before planned early delivery"],
]
story.append(make_table(
    ["Investigation", "When Safe", "Notes"],
    dx_rows, [4.5*cm, 3.5*cm, 9.5*cm], header_bg=MED_BLUE
))
story.append(sp(8))

# ─── MASTER MANAGEMENT TABLE ──────────────────────────────────────────────────
story.append(section_header("4. MASTER MANAGEMENT TABLE: STAGE × TRIMESTER"))
story.append(sp(6))
story.append(info_box(
    "KEY PRINCIPLE: Management must be individualized. Multidisciplinary team (gynecologic oncologist + perinatologist "
    "+ neonatologist + radiation oncologist + psychologist) is MANDATORY for every case. "
    "Lymph node status is the SINGLE most critical factor determining whether pregnancy can be preserved.",
    bg=LIGHT_BLUE, border=MED_BLUE
))
story.append(sp(6))

mgmt_rows = [
    # IA1 no LVSI
    ["IA1\n(No LVSI)",
     "1st (<14 wks)",
     "Observe; avoid conization; repeat colposcopy in 2nd trimester",
     "Cesarean preferred → postpartum Rx"],
    ["IA1\n(No LVSI)",
     "2nd (14–28 wks)",
     "Observe; conize only if cancer cannot be excluded",
     "Cesarean preferred → postpartum Rx"],
    ["IA1\n(No LVSI)",
     "3rd (>28 wks)",
     "Observe to fetal maturity",
     "Cesarean → simple hysterectomy 6 wks postpartum (or conization if fertility desired)"],
    # IA1 LVSI / IA2
    ["IA1 (LVSI+)\nor IA2",
     "1st",
     "SLN biopsy (⁹⁹ᵐTc); if N(−): observe/NACT from 14 wks;\nif N(+): terminate + immediate treatment",
     "C-section + modified radical hysterectomy + pelvic LND at/after delivery"],
    ["IA1 (LVSI+)\nor IA2",
     "2nd",
     "SLN biopsy; if N(−): NACT to delay to ≥32 wks;\nif N(+): immediate chemoradiation",
     "C-section 32–34 wks + radical hysterectomy + LND"],
    ["IA1 (LVSI+)\nor IA2",
     "3rd",
     "Deliver at 32–34 wks when lung maturity confirmed (amniocentesis)",
     "C-section + modified radical hysterectomy + pelvic LND"],
    # IB1-IB2
    ["IB1–IB2\n(≤4 cm)",
     "1st",
     "Option A: Gravid radical hysterectomy + pelvic LND (in situ fetus)\nOption B: SLN → if N(−), NACT from 14 wks → radical trachelectomy (experimental)\nIf N(+): terminate + definitive treatment",
     "Per nodal status; see below"],
    ["IB1–IB2\n(≤4 cm)",
     "2nd (<22 wks)",
     "Gravid radical hysterectomy OR NACT (carboplatin/paclitaxel) from ≥14 wks\nMonitor with MRI q6–8 wks + US q4 wks",
     "C-section ≥32 wks + radical hysterectomy + LND"],
    ["IB1–IB2\n(≤4 cm)",
     "2nd (22–28 wks)",
     "NACT preferred (carboplatin/paclitaxel weekly or q3wk)\nLast cycle ≥3 wks before delivery",
     "C-section 32–34 wks + radical hysterectomy"],
    ["IB1–IB2\n(≤4 cm)",
     "3rd (28–32 wks)",
     "NACT to buy time to ≥32 wks",
     "C-section + radical hysterectomy + LND at same sitting"],
    ["IB1–IB2\n(≤4 cm)",
     "3rd (>32–34 wks)",
     "Deliver promptly (fetal viability assured)",
     "C-section + radical hysterectomy at same sitting"],
    # IB3
    ["IB3\n(>4 cm)",
     "1st/early 2nd",
     "Terminate pregnancy → definitive chemoradiation OR neoadjuvant chemo + surgery",
     "Per non-pregnant IB3 guidelines postpartum"],
    ["IB3\n(>4 cm)",
     "Late 2nd/3rd",
     "NACT bridge; if N(+): terminate + immediate CRT",
     "C-section ≥32 wks → definitive CRT"],
    # IIA
    ["IIA",
     "1st / early 2nd (<22 wks)",
     "Immediate treatment; terminate pregnancy + chemoradiation or radical surgery",
     "Per non-pregnant IIA guidelines"],
    ["IIA",
     "Late 2nd/3rd (>22 wks)",
     "Individualize: NACT bridge if N(−) and patient refuses termination; target ≥32 wks",
     "C-section + definitive CRT postpartum"],
    # IIB-IIIB
    ["IIB–IIIB\n(Locally Advanced)",
     "1st",
     "IMMEDIATE chemoradiation (EBRT + weekly cisplatin 40 mg/m²)\nFetal loss will occur (spontaneous or therapeutic)",
     "N/A — no fetal preservation possible"],
    ["IIB–IIIB\n(Locally Advanced)",
     "2nd (<22 wks)",
     "Immediate treatment; therapeutic termination or wait for spontaneous fetal loss from CRT",
     "Definitive CRT + brachytherapy as non-pregnant"],
    ["IIB–IIIB\n(Locally Advanced)",
     "2nd (>22 wks)",
     "NACT only if patient refuses termination; extreme caution; multidisciplinary decision",
     "Early C-section ≥32 wks → postpartum CRT"],
    ["IIB–IIIB\n(Locally Advanced)",
     "3rd (>28 wks)",
     "Deliver by C-section as soon as viable (≥32 wks preferred)",
     "Begin definitive CRT immediately postpartum"],
    # IVA/IVB
    ["IVA/IVB\n(Metastatic)",
     "Any trimester",
     "Immediate systemic therapy; termination strongly advised; NO delay acceptable",
     "Systemic chemo ± pembrolizumab (post-delivery); RT for pelvic control"],
    ["IVA/IVB\n(Metastatic)",
     "3rd trimester",
     "Deliver by C-section immediately; start systemic therapy without delay",
     "Individualize per PS; palliative intent"],
]

story.append(make_table(
    ["Stage", "Trimester", "Management During Pregnancy", "Definitive Treatment"],
    mgmt_rows,
    [2.5*cm, 2.5*cm, 7*cm, 5.5*cm],
    header_bg=DARK_BLUE
))
story.append(sp(8))

# ─── FLOWCHART 1 ──────────────────────────────────────────────────────────────
story.append(PageBreak())
story.append(section_header("5. FLOWCHART 1 — Initial Assessment & Triage"))
story.append(sp(6))
story.append(flow_box("CERVICAL CANCER DIAGNOSED IN PREGNANCY", bg=DARK_BLUE))
story.append(sp(3)); story.append(flow_arrow()); story.append(sp(3))
story.append(flow_box("MULTIDISCIPLINARY TEAM ASSESSMENT\nGynecologic Oncologist · Perinatologist · Neonatologist · Radiation Oncologist · Psychologist", bg=MED_BLUE))
story.append(sp(3)); story.append(flow_arrow()); story.append(sp(3))

# Two parallel boxes
p1 = flow_box("STAGING\n• MRI pelvis (no gadolinium)\n• CXR + shielding\n• Colposcopy + biopsy\n• SLN biopsy (⁹⁹ᵐTc) if indicated\n• Chest CT if needed", bg=TEAL, w=8.5*cm)
p2 = flow_box("COUNSELING\n• Maternal prognosis\n• Fetal status + gestational age\n• Desire to continue pregnancy\n• Fertility wishes\n• Risks of treatment delay", bg=PURPLE, w=8.5*cm)
two_p = Table([[p1, p2]], colWidths=[8.75*cm, 8.75*cm])
two_p.setStyle(TableStyle([("VALIGN",(0,0),(-1,-1),"TOP"),("LEFTPADDING",(0,0),(-1,-1),2)]))
story.append(two_p)
story.append(sp(3)); story.append(flow_arrow()); story.append(sp(3))
story.append(flow_diamond("KEY DECISION: LYMPH NODE STATUS"))
story.append(sp(3))
story.append(two_col_flow(
    ["NODE NEGATIVE (N−)", "▼", "Pregnancy preservation options open",
     "→ Stage IA–IB2: consider NACT / delay to ≥32 wks",
     "→ Stage ≥IB3: individualize based on trimester"],
    ["NODE POSITIVE (N+)", "▼", "Pregnancy preservation NOT recommended",
     "→ <22 wks: terminate pregnancy",
     "→ >22 wks: early delivery then immediate treatment"],
    label_left="N(−) — Nodes Clear", label_right="N(+) — Nodal Disease"
))
story.append(sp(8))

# ─── FLOWCHART 2 ──────────────────────────────────────────────────────────────
story.append(section_header("6. FLOWCHART 2 — Management by Gestational Age"))
story.append(sp(6))
story.append(flow_box("GESTATIONAL AGE AT DIAGNOSIS", bg=DARK_BLUE))
story.append(sp(3)); story.append(flow_arrow()); story.append(sp(3))

trim_data = [
    [
        flow_box("1st TRIMESTER\n< 14 weeks", bg=RED, w=5.5*cm),
        flow_box("2nd TRIMESTER\n14 – 28 weeks", bg=ORANGE, w=5.5*cm),
        flow_box("3rd TRIMESTER\n> 28 weeks", bg=GREEN, w=5.5*cm),
    ],
    [
        Paragraph("▼", style("Normal",fontSize=14,textColor=RED,alignment=TA_CENTER)),
        Paragraph("▼", style("Normal",fontSize=14,textColor=ORANGE,alignment=TA_CENTER)),
        Paragraph("▼", style("Normal",fontSize=14,textColor=GREEN,alignment=TA_CENTER)),
    ],
    [
        flow_box("IMMEDIATE treatment required\nfor stages >IA1\nOR terminate pregnancy\nif patient consents\n\nSurgery or CRT without delay", bg=RED_LIGHT, tc=RED, w=5.5*cm),
        flow_box("NACT from ≥14 wks\nif N(−) and pregnancy desired\n\nLymph node assessment first\nMonitor MRI q6–8 wks\nLast chemo ≥3 wks before delivery", bg=ORANGE_LIGHT, tc=ORANGE, w=5.5*cm),
        flow_box("Fetal maturity assessment\n(amniocentesis 32–34 wks)\n\nTarget delivery ≥32 wks\nC-section + cancer surgery\nat same sitting if feasible", bg=GREEN_LIGHT, tc=GREEN, w=5.5*cm),
    ]
]
trim_t = Table(trim_data, colWidths=[5.83*cm, 5.83*cm, 5.84*cm])
trim_t.setStyle(TableStyle([
    ("VALIGN",(0,0),(-1,-1),"MIDDLE"),
    ("TOPPADDING",(0,0),(-1,-1),4),
    ("BOTTOMPADDING",(0,0),(-1,-1),4),
]))
story.append(trim_t)
story.append(sp(3)); story.append(flow_arrow()); story.append(sp(3))
story.append(flow_box("DELIVER BY CESAREAN SECTION ≥32 WEEKS\n(Cesarean is strongly preferred mode of delivery for ALL stages — vaginal delivery is most significant predictor of recurrence)", bg=DARK_BLUE))
story.append(sp(3)); story.append(flow_arrow()); story.append(sp(3))
story.append(flow_box("DEFINITIVE STAGE-APPROPRIATE TREATMENT POSTPARTUM\n(Radical hysterectomy + LND  OR  Concurrent chemoradiation  OR  Systemic therapy)\nManage identical to non-pregnant patient", bg=GREY_HEADER))
story.append(sp(8))

# ─── FLOWCHART 3 ──────────────────────────────────────────────────────────────
story.append(section_header("7. FLOWCHART 3 — Stage-Based Algorithm (Summary)"))
story.append(sp(6))

algo_rows = [
    ["Stage IA1 (No LVSI)", LIGHT_BLUE, MED_BLUE,
     "Follow to term (all trimesters)  →  Cesarean (preferred)  →  Postpartum Rx (simple hysterectomy or conization)"],
    ["Stage IA1 (LVSI+) / IA2", TEAL_LIGHT, TEAL,
     "SLN biopsy  →  N(−): delay to term or NACT  →  Cesarean + radical hysterectomy\n                     N(+): terminate + immediate treatment"],
    ["Stage IB1–IB2", LIGHT_BLUE, MED_BLUE,
     "1st trim: Gravid radical hysterectomy OR NACT from 14 wks\n2nd/3rd: NACT  →  Cesarean ≥32 wks  →  Radical hysterectomy + LND"],
    ["Stage IB3–IIA", ORANGE_LIGHT, ORANGE,
     "<22 wks: Terminate + immediate surgery/CRT\n>22 wks: NACT bridge  →  Cesarean ≥32 wks  →  Definitive CRT"],
    ["Stage IIB–IVA (Locally Advanced)", RED_LIGHT, RED,
     "<22 wks: Immediate CRT (terminate / spontaneous loss)\n>28 wks: Deliver early  →  Immediate postpartum CRT\nRegimen: Cisplatin 40 mg/m² weekly + EBRT + brachytherapy"],
    ["Stage IVB (Metastatic)", PURPLE_LIGHT, PURPLE,
     "Terminate pregnancy (any trimester) OR deliver immediately if viable\nSystemic chemotherapy ± pembrolizumab (post-delivery)"],
]
for stage, bg, border, text in algo_rows:
    row_data = [[
        Paragraph(stage, ParagraphStyle("sh", fontName="Helvetica-Bold", fontSize=8.5, textColor=border, leading=12)),
        Paragraph(text, ParagraphStyle("sb", fontName="Helvetica", fontSize=8, textColor=GREY_HEADER, leading=11))
    ]]
    t = Table(row_data, colWidths=[4*cm, 13.5*cm])
    t.setStyle(TableStyle([
        ("BACKGROUND",(0,0),(-1,-1),bg),
        ("BOX",(0,0),(-1,-1),1,border),
        ("TOPPADDING",(0,0),(-1,-1),5),
        ("BOTTOMPADDING",(0,0),(-1,-1),5),
        ("LEFTPADDING",(0,0),(-1,-1),6),
        ("VALIGN",(0,0),(-1,-1),"MIDDLE"),
    ]))
    story.append(t)
    story.append(sp(3))

story.append(sp(6))

# ─── NACT TABLE ───────────────────────────────────────────────────────────────
story.append(PageBreak())
story.append(section_header("8. NEOADJUVANT CHEMOTHERAPY (NACT) IN PREGNANCY"))
story.append(sp(6))
story.append(info_box(
    "ESGO/INCIP 2025: NACT is used to control disease progression and delay delivery until fetal viability (≥32 wks). "
    "Start NO earlier than 14 weeks gestation (organogenesis complete). Last cycle must be ≥3 weeks before planned delivery.",
    bg=LIGHT_BLUE, border=MED_BLUE
))
story.append(sp(5))
nact_rows = [
    ["Earliest start",        "≥14 weeks gestation (after organogenesis)"],
    ["Preferred regimen (ESGO/INCIP 2025)", "Paclitaxel/Carboplatin — weekly OR every-3-week cycles"],
    ["Alternative",           "Cisplatin-based regimens (cisplatin 50–70 mg/m² q3wk ± gemcitabine)"],
    ["Last cycle timing",     "≥3 weeks before planned delivery (bone marrow recovery)"],
    ["Disease monitoring",    "MRI (no gadolinium) q6–8 wks; transvaginal/transrectal US q4 wks"],
    ["Fetal monitoring",      "Standard obstetric protocol; biophysical profile; growth scans"],
    ["Target delivery age",   "≥32 weeks (≥34 weeks ideal)"],
    ["Mode of delivery",      "Cesarean section ALWAYS preferred"],
    ["Main fetal risk",       "Low birth weight; myelosuppression in neonate; avoid <14 wks (teratogenesis)"],
    ["Contraindications",     "Known hypersensitivity; severe hepatic dysfunction; 1st trimester (<14 wks)"],
]
story.append(make_table(["Parameter", "Detail"], nact_rows,
                         [6*cm, 11.5*cm], header_bg=TEAL, alt_bg=TEAL_LIGHT))
story.append(sp(8))

# ─── CHEMO SAFETY TABLE ───────────────────────────────────────────────────────
story.append(section_header("9. CHEMOTHERAPY SAFETY PROFILE IN PREGNANCY"))
story.append(sp(6))
chemo_rows = [
    ["Carboplatin",    "✓ Preferred platinum", "Best tolerated; ESGO/INCIP 2025 first choice"],
    ["Paclitaxel",    "✓ Acceptable ≥14 wks",  "Preferred taxane; limited but acceptable data"],
    ["Cisplatin",     "⚠ Moderate risk",        "Ototoxicity in neonate; usable ≥14 wks; avoid 1st trimester"],
    ["Vincristine",   "⚠ Limited data",         "Avoid 1st trimester; limited cervical ca use"],
    ["Bleomycin",     "⚠ Caution",              "Pulmonary toxicity; limited experience in pregnancy"],
    ["Bevacizumab",   "✗ CONTRAINDICATED",      "Anti-angiogenic; confirmed fetal harm"],
    ["Pembrolizumab", "✗ CONTRAINDICATED",      "Immunotherapy — risk of immune-mediated fetal rejection"],
    ["5-FU",          "✗ Avoid 1st trim",       "Teratogenic in 1st trimester; limited data thereafter"],
]
cs = make_table(
    ["Drug", "Safety", "Notes"],
    chemo_rows, [4*cm, 4*cm, 9.5*cm], header_bg=MED_BLUE
)
# colour the safety cells
for i, row in enumerate(chemo_rows):
    safety = row[1]
    if "✓" in safety: bg = GREEN_LIGHT
    elif "✗" in safety: bg = RED_LIGHT
    else: bg = ORANGE_LIGHT
    cs.setStyle(TableStyle([("BACKGROUND",(1,i+1),(1,i+1), bg)]))
story.append(cs)
story.append(sp(8))

# ─── RADIATION TABLE ──────────────────────────────────────────────────────────
story.append(section_header("10. RADIATION THERAPY IN PREGNANCY"))
story.append(sp(6))
rt_rows = [
    ["1st/2nd trimester — advanced stage", "External beam RT + weekly cisplatin 40 mg/m²; fetal loss anticipated (spontaneous or therapeutic)"],
    ["3rd trimester",                       "AVOID RT; deliver by C-section first; initiate CRT postpartum"],
    ["Brachytherapy",                        "Post-delivery ONLY — never in pregnancy"],
    ["Fetal dose threshold",                 "Deterministic effects >10 cGy; standard CRT doses far exceed this — pregnancy loss is expected"],
    ["Anatomic distortion",                  "Uterine enlargement alters optimal RT field planning; requires specialized dosimetry"],
    ["Concurrent cisplatin",                 "40 mg/m² weekly; gold-standard radiosensitizer; same as non-pregnant protocol"],
]
story.append(make_table(["Situation", "Recommendation"], rt_rows,
                         [6.5*cm, 11*cm], header_bg=RED, alt_bg=RED_LIGHT))
story.append(sp(8))

# ─── MODE OF DELIVERY ─────────────────────────────────────────────────────────
story.append(section_header("11. MODE OF DELIVERY — CRITICAL CONSIDERATIONS"))
story.append(sp(6))
story.append(warn_box(
    "⚠  VAGINAL DELIVERY IS THE MOST SIGNIFICANT INDEPENDENT PREDICTOR OF RECURRENCE  ⚠\n"
    "Multivariate analysis of 56 pregnant women with cervical cancer: recurrences after vaginal delivery\n"
    "predominantly involved DISTANT sites. Cesarean section is STRONGLY preferred for ALL stages."
))
story.append(sp(5))
del_rows = [
    ["Mode of delivery",      "Cesarean section STRONGLY preferred for ALL stages"],
    ["Optimal gestational age","≥32 weeks preferred; ≥34 weeks ideal"],
    ["Cesarean timing",        "At same operative sitting as definitive cancer surgery when feasible"],
    ["Vaginal delivery",       "Only if compelling reason; close inspection of episiotomy site required (metastases reported)"],
    ["Fetal lung maturity",    "Confirm by amniocentesis before planned early delivery (32–34 wks)"],
    ["Concomitant surgery",    "Radical hysterectomy + pelvic LND at C-section if nodes previously staged negative"],
    ["Uterotonic agents",      "Oxytocin preferred; ergometrine use is standard; no specific contraindication"],
]
story.append(make_table(["Consideration", "Recommendation"], del_rows,
                         [6*cm, 11.5*cm], header_bg=TEAL, alt_bg=TEAL_LIGHT))
story.append(sp(8))

# ─── FERTILITY SPARING ────────────────────────────────────────────────────────
story.append(section_header("12. FERTILITY-SPARING OPTIONS (ESGO/ESHRE/ESGE 2024)"))
story.append(sp(6))
fs_rows = [
    ["IA1 (No LVSI)", "Conization / LLETZ", "Negative margins; followed to term; cervical cerclage after conization if needed"],
    ["IA1 (LVSI+) / IA2", "Simple or modified radical trachelectomy", "Nodes negative; tumor ≤2 cm; squamous or adenocarcinoma"],
    ["IB1 (≤2 cm)", "Radical trachelectomy (vaginal or abdominal)", "Nodes negative; no LVSI; specialist center only"],
    ["IB2 (2–4 cm)", "NACT + radical trachelectomy", "EXPERIMENTAL; specialized centers only; limited data"],
    ["Any — N(+)", "NO fertility sparing possible", "Terminate + definitive treatment mandatory"],
    ["Any — LVSI+", "Upgrade management to next stage protocol", "LVSI is an adverse factor requiring lymph node assessment"],
]
story.append(make_table(
    ["Stage", "Procedure", "Conditions / Notes"],
    fs_rows, [2.5*cm, 5*cm, 10*cm], header_bg=PURPLE, alt_bg=PURPLE_LIGHT
))
story.append(sp(8))

# ─── MONITORING ───────────────────────────────────────────────────────────────
story.append(section_header("13. MONITORING DURING CONSERVATIVE MANAGEMENT"))
story.append(sp(6))
mon_rows = [
    ["Clinical exam + colposcopy",          "Every 4–8 weeks during pregnancy"],
    ["MRI pelvis (no gadolinium)",          "Every 6–8 weeks to assess disease progression / NACT response"],
    ["Transvaginal/transrectal ultrasound", "Every 4 weeks (ESGO/INCIP 2025: suitable for NACT response assessment)"],
    ["Fetal wellbeing",                     "Standard obstetric protocol; additional biophysical profiles if NACT administered"],
    ["Fetal growth scans",                  "Every 4 weeks (more frequently if NACT given)"],
    ["Amniocentesis",                       "At 32–34 weeks when planning early delivery to confirm lung maturity"],
    ["Tumor markers (SCC, CEA)",            "Baseline then every 4–6 weeks"],
    ["CBC (if on NACT)",                    "Before each cycle; confirm recovery before next cycle"],
]
story.append(make_table(["Assessment", "Frequency / Notes"], mon_rows,
                         [7*cm, 10.5*cm], header_bg=TEAL, alt_bg=TEAL_LIGHT))
story.append(sp(8))

# ─── POSTPARTUM MANAGEMENT ────────────────────────────────────────────────────
story.append(section_header("14. POSTPARTUM MANAGEMENT BY STAGE"))
story.append(sp(6))
pp_rows = [
    ["IA1 (No LVSI)", "Simple hysterectomy (6 wks postpartum) if no further fertility desired; or conization if fertility desired"],
    ["IA2",           "Modified radical hysterectomy + pelvic lymph node dissection"],
    ["IB1–IB2",       "Radical hysterectomy + pelvic LND ± adjuvant CRT (based on final pathology: Sedlis criteria)"],
    ["IB3–IIA",       "Radical hysterectomy OR definitive CRT per standard non-pregnant guidelines"],
    ["IIB–IVA",       "Concurrent chemoradiation: EBRT + intracavitary brachytherapy + weekly cisplatin 40 mg/m²"],
    ["IVB",           "Systemic chemotherapy ± pembrolizumab (if PD-L1 positive); bevacizumab addition if eligible"],
]
story.append(make_table(["Stage", "Postpartum Treatment"], pp_rows,
                         [2.5*cm, 15*cm], header_bg=GREY_HEADER))
story.append(sp(8))

# ─── SPECIAL SCENARIOS ────────────────────────────────────────────────────────
story.append(section_header("15. SPECIAL CLINICAL SCENARIOS"))
story.append(sp(6))

story.append(Paragraph("Patient Refuses Treatment / Termination", H2))
story.append(info_box(
    "• Document counseling thoroughly; multidisciplinary input mandatory.\n"
    "• NACT from ≥14 wks may bridge to fetal viability.\n"
    "• ESGO/INCIP 2025: 'Delay of therapy is acceptable in carefully selected patients with stage IA–IB2 disease if nodes are negative; "
    "individualize with shared decision-making.'\n"
    "• Maximum safe delay: up to 32 weeks for stage I–II without significant compromise in most published series.",
    bg=YELLOW_LIGHT, border=ORANGE
))
story.append(sp(5))

story.append(Paragraph("Postpartum Diagnosis (Within 6 Months of Delivery)", H2))
story.append(info_box(
    "• Associated with more advanced stage and significantly worse prognosis.\n"
    "• Treat immediately per standard non-pregnant guidelines without delay.\n"
    "• Consider rapid weaning from breastfeeding if systemic therapy required.",
    bg=RED_LIGHT, border=RED
))
story.append(sp(5))

story.append(Paragraph("Advanced Imaging Considerations", H2))
img_rows = [
    ["Abdomen CT (with contrast)", "~2 cGy"],
    ["Pelvis CT (with contrast)",  "~2 cGy"],
    ["Abdomen CT (without)",       "~1 cGy"],
    ["Barium meal (fluoroscopy)",  "~3.9 cGy"],
    ["IVP (fluoroscopy)",          "~0.73 cGy"],
    ["Chest X-ray",               "<0.001 cGy"],
    ["Threshold for deterministic effects", ">10 cGy"],
]
story.append(make_table(
    ["Examination", "Estimated Fetal Dose (1st Trimester)"],
    img_rows, [9*cm, 8.5*cm], header_bg=MED_BLUE
))
story.append(note_box("MRI (without gadolinium) is the imaging modality of choice for local staging in pregnancy. "
                      "Gadolinium crosses the placenta and is CLASS C — avoid unless absolutely essential. "
                      "Source: Creasy & Resnik's Maternal-Fetal Medicine, p. 1352"))
story.append(sp(8))

# ─── QUICK REFERENCE SUMMARY ──────────────────────────────────────────────────
story.append(PageBreak())
story.append(section_header("16. QUICK REFERENCE SUMMARY CARD"))
story.append(sp(6))

qr_headers = ["Stage", "1st Trimester (<14 wks)", "2nd Trimester (14–28 wks)", "3rd Trimester (>28 wks)"]
qr_rows = [
    ["IA1\n(No LVSI)",
     "Observe; colposcopy only",
     "Observe; conize only if essential",
     "Observe to term → C-section → postpartum Rx"],
    ["IA1 (LVSI+)\nIA2",
     "SLN → N(−): observe;\nN(+): terminate + Rx",
     "SLN → N(−): NACT + delay;\nN(+): immediate CRT",
     "Deliver 32–34 wks;\nC-section + radical hyst."],
    ["IB1–IB2",
     "Gravid radical hyst. OR\nNACT from 14 wks",
     "NACT from 14–16 wks;\ndeliver ≥32 wks",
     "NACT → deliver 32–34 wks\n→ radical hysterectomy"],
    ["IB3–IIA",
     "Terminate + surgery/CRT",
     "<22 wks: terminate;\n>22 wks: NACT bridge",
     "Deliver 32–34 wks;\npostpartum CRT"],
    ["IIB–IVA",
     "Terminate + immediate CRT",
     "<22 wks: terminate + CRT;\n>22 wks: NACT bridge if refuses",
     "Deliver early →\nimmediate postpartum CRT"],
    ["IVB",
     "Systemic chemo;\nterminate",
     "Systemic chemo;\ndiscuss pregnancy",
     "Deliver immediately;\nsystemic therapy"],
]
story.append(make_table(qr_headers, qr_rows,
                         [2.5*cm, 4.5*cm, 5.25*cm, 5.25*cm],
                         header_bg=DARK_BLUE))
story.append(sp(8))

# ─── REFERENCES ───────────────────────────────────────────────────────────────
story.append(section_header("17. KEY GUIDELINE REFERENCES"))
story.append(sp(6))
ref_rows = [
    ["1", "ESGO/INCIP 2025", "Amant F et al. ESGO/INCIP Guidelines for management of gynecological cancers during pregnancy. Int J Gynecol Cancer 2025. PMID 40707270"],
    ["2", "ESGO/ESTRO/ESP 2023", "Cibula D et al. ESGO/ESTRO/ESP Guidelines for management of patients with cervical cancer — update 2023. Int J Gynecol Cancer 2023;33:649–66"],
    ["3", "ESGO/ESHRE/ESGE 2024", "Morice P et al. Fertility-sparing treatment in cervical, ovarian cancer and borderline tumours. Lancet Oncol 2024. PMID 39216500"],
    ["4", "FIGO 2018 Staging",   "Bhatla N et al. Revised FIGO staging for carcinoma of the cervix uteri. Int J Gynaecol Obstet 2019;145:129–35"],
    ["5", "NCCN 2024",           "National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology: Cervical Cancer v1.2024"],
    ["6", "Berek & Novak",       "Berek JS, Hacker NF. Berek & Novak's Gynecology, 16th ed. Cervical Cancer During Pregnancy, pp. 2270–2271"],
    ["7", "Creasy & Resnik",     "Creasy & Resnik's Maternal-Fetal Medicine, 8th ed. Cervical Carcinoma in Pregnancy, pp. 1352–1353"],
]
story.append(make_table(
    ["#", "Source", "Full Reference"],
    ref_rows, [0.8*cm, 4.5*cm, 12.2*cm], header_bg=GREY_HEADER
))

story.append(sp(10))
story.append(info_box(
    "DISCLAIMER: These guidelines are intended for educational purposes and clinical reference. "
    "Individual patient management must be decided by a qualified multidisciplinary team, taking into account "
    "the patient's clinical status, institutional resources, and patient preferences. "
    "All cases of CCIP should be centralized to high-volume specialized centers (ESGO/INCIP 2025).",
    bg=YELLOW_LIGHT, border=ORANGE, text_style=NOTE_S
))

# ── Build PDF ─────────────────────────────────────────────────────────────────
doc.build(story)
print("PDF generated:", OUTPUT)